Science.gov

Sample records for age human progress

  1. PROGRESSIVE MECHANICAL BEHAVIOR OF HUMAN CORTICAL BONE IN TENSION FOR TWO AGE GROUPS

    PubMed Central

    Nyman, Jeffry S.; Roy, Anuradha; Reyes, Michael J.; Wang, Xiaodu

    2007-01-01

    The capacity of bone for post-yield energy dissipation decreases with age. To gain information on the cause of such changes, we examined the mechanical behavior of human cadaveric bone as a function of progressive deformation. In this study, tensile specimens from tibiae of 9 middle aged and 8 elderly donors were loaded till failure in an incremental and cyclic (load-dwell-unload-dwell-reload) scheme. The elastic modulus, maximum stress, permanent strain, stress relaxation, viscoelastic time constant, plastic strain energy, elastic release strain energy, and hysteresis energy were determined at incremental strains of each loading cycle. Experimental results showed that elderly bone failed at much lower strains compared to middle aged bone, but little age-related differences were observed in the mechanical behavior of bone until the premature failure of elderly bone. Energy dissipation and permanent strain appeared to linearly increase with increasing strain, while non-linear changes occurred in the modulus loss and stress relaxation/time constant with increasing strain. Such changes suggest that two distinct stages may exist in the progressive deformation of bone. In Stage I, rapid damage accumulation and increased involvement of collagen in load bearing appeared to dominate the mechanical behavior of bone with limited energy dissipation (<20% of total energy dissipated), whereas Stage II is dominated by continuous plastic deformation, accompanied by major energy dissipation through all three pathways till failure. This study suggests that damaging mechanisms in bone vary with deformation and age affects the post-yield mechanisms causing a significant decline in the capacity of aged bone to dissipate energy. PMID:18437693

  2. Progress and Prospects in Human Genetic Research into Age-Related Hearing Impairment

    PubMed Central

    Sugiura, Saiko; Ueda, Hiromi; Nakashima, Tsutomu

    2014-01-01

    Age-related hearing impairment (ARHI) is a complex, multifactorial disorder that is attributable to confounding intrinsic and extrinsic factors. The degree of impairment shows substantial variation between individuals, as is also observed in the senescence of other functions. This individual variation would seem to refute the stereotypical view that hearing deterioration with age is inevitable and may indicate that there is ample scope for preventive intervention. Genetic predisposition could account for a sizable proportion of interindividual variation. Over the past decade or so, tremendous progress has been made through research into the genetics of various forms of hearing impairment, including ARHI and our knowledge of the complex mechanisms of auditory function has increased substantially. Here, we give an overview of recent investigations aimed at identifying the genetic risk factors involved in ARHI and of what we currently know about its pathophysiology. This review is divided into the following sections: (i) genes causing monogenic hearing impairment with phenotypic similarities to ARHI; (ii) genes involved in oxidative stress, biologic stress responses, and mitochondrial dysfunction; and (iii) candidate genes for senescence, other geriatric diseases, and neurodegeneration. Progress and prospects in genetic research are discussed. PMID:25140308

  3. iPLA2• Knockout Mouse, a Genetic Model for Progressive Human Motor Disorders, Develops Age-Related Neuropathology

    PubMed Central

    Blanchard, Helene; Taha, Ameer Y.; Cheon, Yewon; Kim, Hyung-Wook; Turk, John; Rapoport, Stanley I.

    2015-01-01

    Calcium-independent phospholipase A2 group VIa (iPLA2β) preferentially releases docosahexaenoic acid (DHA) from the sn-2 position of phospholipids. Mutations of its gene, PLA2G6, are found in patients with several progressive motor disorders, including Parkinson disease. At 4 months, PLA2G6 knockout mice (iPLA2β−/−) show minimal neuropathology but altered brain DHA metabolism. By 1 year, they develop motor disturbances, cerebellar neuronal loss, and striatal α-synuclein accumulation. We hypothesized that older iPLA2β−/− mice also would exhibit inflammatory and other neuropathological changes. Real-time polymerase chain reaction and Western blotting were performed on whole brain homogenate from 15 to 20-month old male iPLA2β−/− or wild-type (WT) mice. These older iPLA2β−/− mice compared with WT showed molecular evidence of microglial (CD-11b, iNOS) and astrocytic (glial fibrillary acidic protein) activation, disturbed expression of enzymes involved in arachidonic acid metabolism, loss of neuroprotective brain derived neurotrophic factor, and accumulation of cytokine TNF-α messenger ribonucleic acid, consistent with neuroinflammatory pathology. There was no evidence of synaptic loss, of reduced expression of dopamine active reuptake transporter, or of accumulation of the Parkinson disease markers Parkin or Pink1. iPLA2γ expression was unchanged. iPLA2β deficient mice show evidence of neuroinflammation and associated neuropathology with motor dysfunction in later life. These pathological biomarkers could be used to assess efficacy of dietary intervention, antioxidants or other therapies on disease progression in this mouse model of progressive human motor diseases associated with a PLA2G6 mutation. PMID:24919816

  4. Auto-catalysed progression of aneuploidy explains the Hayflick limit of cultured cells, carcinogen-induced tumours in mice, and the age distribution of human cancer.

    PubMed Central

    Rasnick, D

    2000-01-01

    Evidence continues to accumulate that aneuploidy, an imbalance in the number of chromosomes, is responsible for the characteristic phenotypes of cancer, including the abnormal cellular size and morphology of cancer cells, the appearance of tumour-associated antigens, as well as the high levels of membrane-bound and secreted proteins responsible for invasiveness and loss of contact inhibition. Aneuploidy has also been demonstrated to be the self-perpetuating source of the karyotypic instability of cancer cells. Here it is shown that the auto-catalysed progression of aneuploidy explains the kinetics of the finite lifetime of diploid cells in culture, the time course of the appearance of papillomas and carcinomas in benzo[a]pyrene-treated mice, and the age-dependence of human cancers. Modelling studies indicate that the ease of spontaneous transformation of mouse cells in culture may be due to a chaotic progression of aneuploidy. Conversely, the strong preference towards senescence and resistance to transformation of human cells in culture may be the result of a non-chaotic progression of aneuploidy. Finally, a method is proposed for quantifying the aneuploidogenic potencies of carcinogens. PMID:10839979

  5. Sleep and Human Aging.

    PubMed

    Mander, Bryce A; Winer, Joseph R; Walker, Matthew P

    2017-04-05

    Older adults do not sleep as well as younger adults. Why? What alterations in sleep quantity and quality occur as we age, and are there functional consequences? What are the underlying neural mechanisms that explain age-related sleep disruption? This review tackles these questions. First, we describe canonical changes in human sleep quantity and quality in cognitively normal older adults. Second, we explore the underlying neurobiological mechanisms that may account for these human sleep alterations. Third, we consider the functional consequences of age-related sleep disruption, focusing on memory impairment as an exemplar. We conclude with a discussion of a still-debated question: do older adults simply need less sleep, or rather, are they unable to generate the sleep that they still need?

  6. Progress and privilege: America in the age of environmentalism

    SciTech Connect

    Tucker, W.

    1982-01-01

    Environmentalism, which was a rarity in the 1960s, approaches a national religion in the 1980s, with some environmentalists experiencing pleasure at the prospect of limited resources and no growth. The author explores this new ambivalence toward progress, and concludes that accomplishment can dampen ambition. His analysis of environmentalism as an expression of privilege examines the political and economic characteristics of environmentalists, the major environmental issues, and the public revolt against science to uncover an aristocratic element that is diappearing from our culture. Progress will continue, however, because of global ambitions. The US can build on what has been learned during the Age of Environmentalism and get on with the progress of humanity. 159 references, 1 figure. (DCK)

  7. iPSC technology to study human aging and aging-related disorders.

    PubMed

    Liu, Guang-Hui; Ding, Zhichao; Izpisua Belmonte, Juan Carlos

    2012-12-01

    A global aging population, normally accompanied by a high incidence of aging-associated diseases, has prompted a renewed interest in basic research on human aging. Although encouraging progress has been achieved using animal models, the underlying fundamental mechanisms of aging remain largely unknown. Here, we review the human induced pluripotent stem cell (hiPSC)-based models of aging and aging-related diseases. These models seek to advance our knowledge of aging molecular mechanisms and help to develop strategies for treating aging-associated human diseases.

  8. Age progressive volcanism in the Tasmantid Seamounts

    NASA Astrophysics Data System (ADS)

    McDougall, Ian; Duncan, Robert A.

    1988-07-01

    The Tasmantid Seamounts comprise a northerly trending linear chain of submarine volcanoes that extend over more than 1300 km in the middle of the Tasman Basin, located to the east of the Australian continental margin. The volcanoes are situated upon deep oceanic crust of Late Cretaceous/Early Cenozoic age. Several of the volcanoes were built from sea floor depths of more than 4000 m to above sea level, and were then eroded to flat-topped mountains which have subsided to depths as great as 400 m. Basalt samples dredged from Gascoyne, Taupo, Derwent Hunter, Britannia and Queensland Seamounts have been dated by the K-Ar and 40Ar/ 39Ar methods, yielding results in the range 24 to 6.4 Ma, Early to Late Miocene. A progressive younging of the volcanism southward along the seamount chain at an average rate of 67 ± 5mm/year is indicated. The predicted present position of the volcanic focus is at 40.4°S latitude, and between 155° and 156°E longitude, virtually coincident with the epicentre of a recent large earthquake. These results provide strong evidence that the Tasmantid Seamounts represent a hotspot track, effectively recording motion of the Australian plate across the sublithospheric mantle source region for the volcanism. Comparison with results from hotspot traces on the same plate and on the African plate further demonstrate that these hotspots provide a useful frame of reference for plate motions, and that relative movement between individual hotspots must be less than about 5 mm/year.

  9. Progress towards the 'Golden Age' of biotechnology.

    PubMed

    Gartland, K M A; Bruschi, F; Dundar, M; Gahan, P B; Viola Magni, M p; Akbarova, Y

    2013-07-01

    Biotechnology uses substances, materials or extracts derived from living cells, employing 22 million Europeans in a € 1.5 Tn endeavour, being the premier global economic growth opportunity this century. Significant advances have been made in red biotechnology using pharmaceutically and medically relevant applications, green biotechnology developing agricultural and environmental tools and white biotechnology serving industrial scale uses, frequently as process feedstocks. Red biotechnology has delivered dramatic improvements in controlling human disease, from antibiotics to overcome bacterial infections to anti-HIV/AIDS pharmaceuticals such as azidothymidine (AZT), anti-malarial compounds and novel vaccines saving millions of lives. Green biotechnology has dramatically increased food production through Agrobacterium and biolistic genetic modifications for the development of 'Golden Rice', pathogen resistant crops expressing crystal toxin genes, drought resistance and cold tolerance to extend growth range. The burgeoning area of white biotechnology has delivered bio-plastics, low temperature enzyme detergents and a host of feedstock materials for industrial processes such as modified starches, without which our everyday lives would be much more complex. Biotechnological applications can bridge these categories, by modifying energy crops properties, or analysing circulating nucleic acid elements, bringing benefits for all, through increased food production, supporting climate change adaptation and the low carbon economy, or novel diagnostics impacting on personalized medicine and genetic disease. Cross-cutting technologies such as PCR, novel sequencing tools, bioinformatics, transcriptomics and epigenetics are in the vanguard of biotechnological progress leading to an ever-increasing breadth of applications. Biotechnology will deliver solutions to unimagined problems, providing food security, health and well-being to mankind for centuries to come.

  10. Biological psychological and social determinants of old age: bio-psycho-social aspects of human aging.

    PubMed

    Dziechciaż, Małgorzata; Filip, Rafał

    2014-01-01

    The aging of humans is a physiological and dynamic process ongoing with time. In accordance with most gerontologists' assertions it starts in the fourth decade of life and leads to death. The process of human aging is complex and individualized, occurs in the biological, psychological and social sphere. Biological aging is characterized by progressive age-changes in metabolism and physicochemical properties of cells, leading to impaired self-regulation, regeneration, and to structural changes and functional tissues and organs. It is a natural and irreversible process which can run as successful aging, typical or pathological. Biological changes that occur with age in the human body affect mood, attitude to the environment, physical condition and social activity, and designate the place of seniors in the family and society. Psychical ageing refers to human awareness and his adaptability to the ageing process. Among adaptation attitudes we can differentiate: constructive, dependence, hostile towards others and towards self attitudes. With progressed age, difficulties with adjustment to the new situation are increasing, adverse changes in the cognitive and intellectual sphere take place, perception process involutes, perceived sensations and information received is lowered, and thinking processes change. Social ageing is limited to the role of an old person is culturally conditioned and may change as customs change. Social ageing refers to how a human being perceives the ageing process and how society sees it.

  11. Progress in Aging Epidemiology in Japan: The JAGES Project

    PubMed Central

    Kondo, Katsunori

    2016-01-01

    Aging is a prominent topic in global health. The purpose of this report is to document progress in two of our research projects in Japan, which currently is the most aged society in the world. The Japan Gerontological Evaluation Study (JAGES) is one of the largest nation-wide research projects on aging, with more than 100 000 participants in 2010 and 2013. One of the notable findings is that community participation is a significant determinant of older people’s health. We have also made progress in the development of the JAGES Health Equity Assessment and Response Tools (HEART), which is a management tool for developing age-friendly cities. This progress suggests that community perspective and management of health promotion in the communities are valuable and require further research. PMID:27349200

  12. Progress in Aging Epidemiology in Japan: The JAGES Project.

    PubMed

    Kondo, Katsunori

    2016-07-05

    Aging is a prominent topic in global health. The purpose of this report is to document progress in two of our research projects in Japan, which currently is the most aged society in the world. The Japan Gerontological Evaluation Study (JAGES) is one of the largest nation-wide research projects on aging, with more than 100 000 participants in 2010 and 2013. One of the notable findings is that community participation is a significant determinant of older people's health. We have also made progress in the development of the JAGES Health Equity Assessment and Response Tools (HEART), which is a management tool for developing age-friendly cities. This progress suggests that community perspective and management of health promotion in the communities are valuable and require further research.

  13. When age-progressed images are unreliable: The roles of external features and age range.

    PubMed

    Erickson, William Blake; Lampinen, James Michael; Frowd, Charlie D; Mahoney, Gregory

    2017-03-01

    When children go missing for many years, investigators commission age-progressed images from forensic artists to depict an updated appearance. These images have anecdotal success, and systematic research has found they lead to accurate recognition rates comparable to outdated photos. The present study examines the reliability of age progressions of the same individuals created by different artists. Eight artists first generated age progressions of eight targets across three age ranges. Eighty-five participants then evaluated the similarity of these images against other images depicting the same targets progressed at the same age ranges, viewing either whole faces or faces with external features concealed. Similarities were highest over shorter age ranges and when external features were concealed. Implications drawn from theory and application are discussed.

  14. Aging of oocyte, ovary, and human reproduction.

    PubMed

    Ottolenghi, Chris; Uda, Manuela; Hamatani, Toshio; Crisponi, Laura; Garcia, Jose-Elias; Ko, Minoru; Pilia, Giuseppe; Sforza, Chiarella; Schlessinger, David; Forabosco, Antonino

    2004-12-01

    We review age-related changes in the ovary and their effect on female fertility, with particular emphasis on follicle formation, follicle dynamics, and oocyte quality. The evidence indicates that the developmental processes leading to follicle formation set the rules determining follicle quiescence and growth. This regulatory system is maintained until menopause and is directly affected in at least some models of premature ovarian failure (POF), most strikingly in the Foxl2 mouse knockout, a model of human POF with monogenic etiology (blepharophimosis/ptosis/epicanthus inversus syndrome). Several lines of evidence indicate that if the ovarian germ cell lineage maintains regenerative potential, as recently suggested in the mouse, a role in follicle dynamics for germ stem cells, if any, is likely indirect or secondary. In addition, age-related variations in oocyte quality in animal models suggest that reproductive competence is acquired progressively and might depend on parallel growth and differentiation of follicle cells and stroma. Genomewide analyses of the mouse oocyte transcriptome have begun to be used to systematically investigate the mechanisms of reproductive competence that are altered with aging. Investigative and therapeutic strategies can benefit from considering the role of continuous interactions between follicle cells and oocytes from the beginning of histogenesis to full maturation.

  15. Age and progression of volcanism, Wrangell volcanic field, Alaska

    USGS Publications Warehouse

    Richter, D.H.; Smith, James G.; Lanphere, M.A.; Dalrymple, G.B.; Reed, B.L.; Shew, N.

    1990-01-01

    The Wrangell volcanic field covers more than 10 000 km2 in southern Alaska and extends uninterrupted into northwest. Yukon Territory. Lavas in the field exhibit medium-K, calc-alkaline affinities, typical of continental volcanic arcs along convergent plate margins. Eleven major eruptive centers are recognized in the Alaskan part of the field. More than 90 K-Ar age determinations in the field show a northwesterly progression of eruptive activity from 26 Ma, near the Alaska-Yukon border, to about 0.2 Ma at the northwest end of the field. A few age determinations in the southeast extension of the field in Yukon Territory, Canada, range from 11 to 25 Ma. The ages indicate that the progression of volcanism in the Alaska part of the field increased from about 0.8 km/Ma, at 25 Ma, to more than 20 km/MA during the past 2 Ma. The progression of volcanic activity and its increased rate of migration with time is attributed to changes in the rate and angle of Pacific plate convergence and the progressive decoupling of the Yakutat terrane from North America. Subduction of Yakutat terrane-Pacific plate and Wrangell volcanic activity ceased about 200 000 years age when Pacific plate motion was taken up by strike-slip faulting and thrusting. ?? 1990 Springer-Verlag.

  16. [Experimental models of human skin aging].

    PubMed

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

    2016-02-01

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

  17. Ageing of the human hypothalamus.

    PubMed

    Swaab, D F

    1995-01-01

    The various hypothalamic nuclei show very different patterns of change in ageing. These patterns are a basis for changes in biological rhythms, hormones, autonomous functions or behavior. The suprachiasmatic nucleus (SCN) coordinates circadian and circannual rhythms. A marked seasonal and circadian variation in the vasopressin (AVP) cell number of the SCN was observed in relation to the variation in photoperiod. During normal ageing, the circadian variation and number of AVP-expressing neurons in the SCN decreases. The sexually dimorphic nucleus (SDN), intermediate nucleus or INAH-1 is localized between the supraoptic and paraventricular nucleus (PVN). In adult men the SDN is twice as large as in adult women. In girls, the SDN shows a first period of decreasing cell numbers during prepubertal development, leading to sexual dimorphism. During ageing a decrease in cell number is found in both sexes. The cells of the supraoptic nucleus and PVN produce AVP or oxytocin and coexpress tyrosine hydroxylase. These nuclei are examples of neuron populations that seem to stay perfectly intact in ageing. Parvicellular corticotropin-releasing-hormone (CRH)-containing neurons are found throughout the PVN. CRH neurons in the PVN are activated in the course of ageing, as indicated by their increase in number and AVP coexpression. Part of the infundibular (or arcuate) nucleus, the subventricular nucleus, contains hypertrophic neurons in postmenopausal women. The hypertrophied neurons contain neurokinin-B (NKB), substance P and estrogen receptors and probably act on LHRH neurons as interneurons. The NKB neurons may also be involved in the initiation of menopausal flushes. The nucleus tuberalis lateralis might be involved in feeding behavior and metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. The Impact of Aging on Human Sexuality.

    ERIC Educational Resources Information Center

    Rienzo, Barbara A.

    1985-01-01

    Lay persons and professionals need to be educated on the effects of aging on human sexuality. Effective communication techniques and accurate sexuality information can lead to prevention of psychosocial problems and sexual dysfunction. (Author/DF)

  19. Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging

    PubMed Central

    Quan, Taihao; Fisher, Gary J

    2015-01-01

    Human skin is largely composed of a collagen-rich connective tissue, which provides structural and functional support. The collagen-rich connective tissue is produced, organized, and maintained by dermal fibroblasts. During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of collagen fibrils impairs skin structure and function and creates a tissue microenvironment that promotes age-related skin diseases, such as delayed wound healing and skin cancer development. This review describes cellular mechanisms that give rise to self-perpetuating, collagen fibril fragmentation that creates an age-associated dermal microenvironment (AADM), which contributes to decline of human skin function. PMID:25660807

  20. Relationship between Human Aging Muscle and Oxidative System Pathway

    PubMed Central

    Doria, Enrico; Buonocore, Daniela; Focarelli, Angela; Marzatico, Fulvio

    2012-01-01

    Ageing is a complex process that in muscle is usually associated with a decrease in mass, strength, and velocity of contraction. One of the most striking effects of ageing on muscle is known as sarcopenia. This inevitable biological process is characterized by a general decline in the physiological and biochemical functions of the major systems. At the cellular level, aging is caused by a progressive decline in mitochondrial function that results in the accumulation of reactive oxygen species (ROS) generated by the addition of a single electron to the oxygen molecule. The aging process is characterized by an imbalance between an increase in the production of reactive oxygen species in the organism and the antioxidant defences as a whole. The goal of this review is to examine the results of existing studies on oxidative stress in aging human skeletal muscles, taking into account different physiological factors (sex, fibre composition, muscle type, and function). PMID:22685621

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  2. Progressive age-associated activation of JNK associates with conduction disruption in the aged atrium.

    PubMed

    Jones, Sandra A; Lancaster, Matthew K

    2015-03-01

    Connexin43 (Cx43) is critical for maintaining electrical conduction across atrial muscle. During progressive ageing atrial conduction slows associating with increasing susceptibility to arrhythmias. Changes in Cx43 protein expression, or its phosphorylation status, can instigate changes in the conduction of the cardiac action potential. This study investigated whether increased levels of activated c-jun N-terminal kinase (JNK) is responsible for the decline of Cx43 during ageing. Right atria from guinea pigs aged between 1 day and 38 months of age were examined. The area of the intercalated disc increased with age concurrent with a 75% decline in C43 protein expression. An age-dependent increase in activated-JNK correlated with a rise in phosphorylated Cx43, but also slowing of action potential conduction velocity across the atria from 0.38±0.01 m/s at 1 month of age to 0.30±0.01 m/s at 38 months. The JNK activator anisomycin increased activated JNK in myocytes and reduced Cx43 protein expression simulating ageing. The JNK inhibitor SP600125, was found to eradicate almost all trace of Cx43 protein. We conclude that in vivo activation of JNK increases with age leading to the loss of Cx43 protein resulting in impaired conduction and contributing to the increasing risk of atrial arrhythmias with advancing age.

  3. [Physiological features of skin ageing in human].

    PubMed

    Tikhonova, I V; Tankanag, A V; Chemeris, N K

    2013-01-01

    The issue deals with the actual problem of gerontology, notably physiological features of human skin ageing. In the present review the authors have considered the kinds of ageing, central factors, affected on the ageing process (ultraviolet radiation and oxidation stress), as well as the research guidelines of the ageing changes in the skin structure and fuctions: study of mechanical properties, microcirculation, pH and skin thickness. The special attention has been payed to the methods of assessment of skin blood flow, and to results of investigations of age features of peripheral microhemodynamics. The laser Doppler flowmetry technique - one of the modern, noninvasive and extensively used methods for the assessmant of skin blood flow microcirculation system has been expanded in the review. The main results of the study of the ageing changes of skin blood perfusion using this method has been also presented.

  4. [Age and aging as incomplete architecture of human ontogenesis].

    PubMed

    Baltes, P B

    1999-12-01

    The focus is on the basic biological-genetic and social-cultural architecture of human development across the life span. The starting point is the frame provided by past evolutionary forces. A first conclusion is that for modern times and the relative brevity of the time windows involved in modernity, further change in human functioning is primarily dependent on the evolution of new cultural forms of knowledge rather than evolution-based changes in the human genome. A second conclusion concerns the general architecture of the life course. Three governing lifespan developmental principles coexist. First, because long-term evolutionary selection evince a negative age correlation, genome-based plasticity and biological potential decrease with age. Second, for growth aspects of human development to extend further into the life span, culture-based resources are required at ever increasing levels. Third, because of age-related losses in biological plasticity and negative effects associated with some principles of learning (e.g., negative transfer), the efficiency of culture is reduced as lifespan development unfolds. Joint application of these principles suggests that the lifespan architecture becomes more and more incomplete with age. Three examples are given to illustrate the implications of the lifespan architecture outlined. The first is a general theory of development involving the orchestration of three component processes and their age-related dynamics: Selection, optimization, and compensation. The second example is theory and research on lifespan intelligence that distinguishes between the biology-based mechanics and culture-based pragmatics of intelligence and specifies distinct age gradients for the two categories of intellectual functioning. The third example considers the goal of evolving a positive biological and cultural scenario for the last phase of life (fourth age). Because of the general lifespan architecture outlined, this objective becomes

  5. Protein Oxidation in Aging: Does It Play a Role in Aging Progression?

    PubMed Central

    Reeg, Sandra

    2015-01-01

    Abstract Significance: A constant accumulation of oxidized proteins takes place during aging. Oxidation of proteins leads to a partial unfolding and, therefore, to aggregation. Protein aggregates impair the activity of cellular proteolytic systems (proteasomes, lysosomes), resulting in further accumulation of oxidized proteins. In addition, the accumulation of highly crosslinked protein aggregates leads to further oxidant formation, damage to macromolecules, and, finally, to apoptotic cell death. Furthermore, protein oxidation seems to play a role in the development of various age-related diseases, for example, neurodegenerative diseases. Recent Advances: The highly oxidized lipofuscin accumulates during aging. Lipofuscin formation might cause impaired lysosomal and proteasomal degradation, metal ion accumulation, increased reactive oxygen species formation, and apoptosis. Critical Issues: It is still unclear to which extent protein oxidation is involved in the progression of aging and in the development of some age-related diseases. Future Directions: An extensive knowledge of the effects of protein oxidation on the aging process and its contribution to the development of age-related diseases could enable further strategies to reduce age-related impairments. Strategies aimed at lowering aggregate formation might be a straightforward intervention to reduce age-related malfunctions of organs. Antioxid. Redox Signal. 23, 239–255. PMID:25178482

  6. Aging of the human ovary and testis.

    PubMed

    Perheentupa, Antti; Huhtaniemi, Ilpo

    2009-02-05

    Aging is associated with structural and functional alterations in all organs of the human body. The aging of gonads represents in this respect a special case, because these organs are not functional for the whole lifespan of an individual and their normal function is not indispensable for functions of the rest of the body. Ovarian function lasts for the reproductive life of a woman, i.e., from menarche until menopause. The testicular endocrine function, in contrast, begins already in utero, is interrupted between neonatal life and puberty, and continues thereafter along with spermatogenesis, with only slight decline, until old age. The aging processes of the ovary and testis are therefore very different. We describe in this review the structural and functional alterations in the human ovary and testis upon aging. Special emphasis will be given to clinically significant alterations, which in women concern the causes and consequences of the individual variability of fertility during the latter part of the reproductive age. The clinically important aspect of testicular aging entails the decline of androgen production in aging men.

  7. The impact of aging on human sexuality.

    PubMed

    Rienzo, B A

    1985-02-01

    Review of gerontological and medical literature reveals the need for education for lay persons and professionals about the effects of the aging process on human sexuality. Primary prevention of psychosocial problems and sexual dysfunction could be abated by including accurate information about sexuality and aging and effective communication techniques in sexuality education programs, including those with young adults. In addition, professional preparation of health educators must include the skills and knowledge needed in this area.

  8. Glutathione dysregulation and the etiology and progression of human diseases

    PubMed Central

    Ballatori, Nazzareno; Krance, Suzanne M.; Notenboom, Sylvia; Shi, Shujie; Tieu, Kim; Hammond, Christine L.

    2009-01-01

    Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and as a result, disturbances in GSH homeostasis are implicated in the etiology and/or progression of a number of human diseases, including cancer, diseases of aging, cystic fibrosis, and cardiovascular, inflammatory, immune, metabolic, and neurodegenerative diseases. Because of GSH’s pleiotropic effects on cell functions, it has been quite difficult to define the role of GSH in the onset and/or the expression of human diseases, although significant progress is being made. GSH levels, turnover rates and/or oxidation state can be compromised by inherited or aquired defects in the enzymes, transporters, signaling molecules, or transcription factors that are involved in its homeostasis, or from exposure to reactive chemicals or metabolic intermediates. GSH deficiency or a decrease in the GSH/glutathione disulfide (GSSG) ratio manifests itself largely through an increased susceptibility to oxidative stress, and the resulting damage is thought to be involved in diseases such as cancer, Parkinson’s disease, and Alzheimer’s disease. In addition, imbalances in GSH levels affect immune system function, and are thought to play a role in the aging process. Just as low intracellular GSH levels decrease cellular antioxidant capacity, elevated GSH levels generally increase antioxidant capacity and resistance to oxidative stress, and this is observed in many cancer cells. The higher GSH levels in some tumor cells are also typically associated with higher levels of GSH-related enzymes and transporters. Although neither the mechanism nor the implications of these changes are well defined, the high GSH content makes cancer cells chemoresistant, which is a major factor that limits drug treatment. The present report highlights and integrates the growing connections between imbalances in GSH homeostasis and a multitude of human diseases

  9. Accelerated aging syndromes, are they relevant to normal human aging?

    PubMed

    Dreesen, Oliver; Stewart, Colin L

    2011-09-01

    Hutchinson-Gilford Progeria (HGPS) and Werner syndromes are diseases that clinically resemble some aspects of accelerated aging. HGPS is caused by mutations in theLMNA gene resulting in post-translational processing defects that trigger Progeria in children. Werner syndrome, arising from mutations in the WRN helicase gene, causes premature aging in young adults. What are the molecular mechanism(s) underlying these disorders and what aspects of the diseases resemble physiological human aging? Much of what we know stems from the study of patient derived fibroblasts with both mutations resulting in increased DNA damage, primarily at telomeres. However, in vivo patients with Werner's develop arteriosclerosis, among other pathologies. In HGPS patients, including iPS derived cells from HGPS patients, as well as some mouse models for Progeria, vascular smooth muscle (VSM) appears to be among the most severely affected tissues. Defective Lamin processing, associated with DNA damage, is present in VSM from old individuals, indicating processing defects may be a factor in normal aging. Whether persistent DNA damage, particularly at telomeres, is the root cause for these pathologies remains to be established, since not all progeroid Lmna mutations result in DNA damage and genome instability.

  10. DNA methylation and healthy human aging.

    PubMed

    Jones, Meaghan J; Goodman, Sarah J; Kobor, Michael S

    2015-12-01

    The process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next-generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site-specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age-related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining 'epigenetic age' for human health and outline some important caveats to existing and future studies.

  11. Aging-associated changes in human brain.

    PubMed

    Mrak, R E; Griffin, S T; Graham, D I

    1997-12-01

    A wide variety of anatomic and histological alterations are common in brains of aged individuals. However, identification of intrinsic aging changes--as distinct from changes resulting from cumulative environmental insult--is problematic. Some degree of neuronal and volume loss would appear to be inevitable, but recent studies have suggested that the magnitudes of such changes are much less than previously thought, and studies of dendritic complexity in cognitively intact individuals suggest continuing neuronal plasticity into the eighth decade. A number of vascular changes become more frequent with age, many attributable to systemic conditions such as hypertension and atherosclerosis. Age-associated vascular changes not clearly linked to such conditions include hyaline arteriosclerotic changes with formation of arterial tortuosities in small intracranial vessels and the radiographic changes in deep cerebral white matter known as "leukoaraiosis." Aging is accompanied by increases in glial cell activation, in oxidative damage to proteins and lipids, in irreversible protein glycation, and in damage to DNA, and such changes may underlie in part the age-associated increasing incidence of "degenerative" conditions such as Alzheimer disease and Parkinson disease. A small number of histological changes appear to be universal in aged human brains. These include increasing numbers of corpora amylacea within astrocytic processes near blood-brain or cerebrospinal fluid-brain interfaces, accumulation of the "aging" pigment lipofuscin in all brain regions, and appearance of Alzheimer-type neurofibrillary tangles (but not necessarily amyloid plaques) in mesial temporal structures.

  12. Obesity accelerates epigenetic aging of human liver.

    PubMed

    Horvath, Steve; Erhart, Wiebke; Brosch, Mario; Ammerpohl, Ole; von Schönfels, Witigo; Ahrens, Markus; Heits, Nils; Bell, Jordana T; Tsai, Pei-Chien; Spector, Tim D; Deloukas, Panos; Siebert, Reiner; Sipos, Bence; Becker, Thomas; Röcken, Christoph; Schafmayer, Clemens; Hampe, Jochen

    2014-10-28

    Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an "epigenetic clock") to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10(-4) in dataset 1 and r = 0.42, P = 1.2 × 10(-4) in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10(-9)) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer.

  13. Aged Garlic Extract Modifies Human Immunity.

    PubMed

    Percival, Susan S

    2016-02-01

    Garlic contains numerous compounds that have the potential to influence immunity. Immune cells, especially innate immune cells, are responsible for the inflammation necessary to kill pathogens. Two innate lymphocytes, γδ-T and natural killer (NK) cells, appear to be susceptible to diet modification. The purpose of this review was to summarize the influence of aged garlic extract (AGE) on the immune system. The author's laboratory is interested in AGE's effects on cell proliferation and activation and inflammation and to learn whether those changes might affect the occurrence and severity of colds and flu. Healthy human participants (n = 120), between 21 and 50 y of age, were recruited for a randomized, double-blind, placebo-controlled parallel-intervention study to consume 2.56 g AGE/d or placebo supplements for 90 d during the cold and flu season. Peripheral blood mononuclear cells were isolated before and after consumption, and γδ-T and NK cell function was assessed by flow cytometry. The effect on cold and flu symptoms was determined by using daily diary records of self-reported illnesses. After 45 d of AGE consumption, γδ-T and NK cells proliferated better and were more activated than cells from the placebo group. After 90 d, although the number of illnesses was not significantly different, the AGE group showed reduced cold and flu severity, with a reduction in the number of symptoms, the number of days participants functioned suboptimally, and the number of work/school days missed. These results suggest that AGE supplementation may enhance immune cell function and may be partly responsible for the reduced severity of colds and flu reported. The results also suggest that the immune system functions well with AGE supplementation, perhaps with less accompanying inflammation. This trial was registered at clinicaltrials.gov as NCT01390116.

  14. Age-progressive volcanism in the Tasman and Coral seas

    NASA Astrophysics Data System (ADS)

    Williams, S.; Gans, P. B.; Mortimer, N. N.; Meffre, S.; Seton, M.

    2014-12-01

    The South West Pacific is the site of widespread Cenozoic volcanism, much of which has formed without a clear spatio-temporal pattern. Exceptions to this overall trend are found in the Tasman Sea, where two chains of age-progressive volcanism are present, the Tasmantids and the Lord Howe seamount chain (LHSC). Both of these follow broadly north-south co-linear trends, recording rapid northwards motion of the Australian plate since >24 Ma. The bathymetric expression of the volcanic trails can be traced northwards towards the Coral Sea, which hosts a complex tapestry of poorly sampled plateaux and rises whose relationship to hotspot volcanism remains enigmatic. We present the results of a marine geophysical and dredging survey to the eastern Coral Sea onboard the RV Southern Surveyor in October-November, 2012. We constrain the timing of basin opening in the South Rennell Trough and Santa Cruz Basin to between ~43-28 Ma, using a combination of magnetic anomaly profiles, seafloor fabric from swath bathymetry data, Ar-Ar dating of basalts and paleontological dating of carbonates. The evolution of this spreading system corresponds to the opening of the Solomon Sea further north, where chrons 19-16 have been identified, suggesting the existence of a single > 2,000 km long back-arc basin. Rocks dredged from the northernmost volcanoes of the LHSC, close to the southern end of the South Rennell Trough, are dated at ~27-28 Ma. Geochemically the LHSC lavas are intraplate tholeiites and contrast with older E-MORB-type basalts formed at the ultra-slow spreading South Rennell Trough until ~28 Ma. These are the oldest rocks recovered from the LHSC, and their age confirms predictions from absolute plate motion modeling.

  15. Human serum metabolic profiles are age dependent

    PubMed Central

    Yu, Zhonghao; Zhai, Guangju; Singmann, Paula; He, Ying; Xu, Tao; Prehn, Cornelia; Römisch-Margl, Werner; Lattka, Eva; Gieger, Christian; Soranzo, Nicole; Heinrich, Joachim; Standl, Marie; Thiering, Elisabeth; Mittelstraß, Kirstin; Wichmann, Heinz-Erich; Peters, Annette; Suhre, Karsten; Li, Yixue; Adamski, Jerzy; Spector, Tim D; Illig, Thomas; Wang-Sattler, Rui

    2012-01-01

    Understanding the complexity of aging is of utmost importance. This can now be addressed by the novel and powerful approach of metabolomics. However, to date, only a few metabolic studies based on large samples are available. Here, we provide novel and specific information on age-related metabolite concentration changes in human homeostasis. We report results from two population-based studies: the KORA F4 study from Germany as a discovery cohort, with 1038 female and 1124 male participants (32–81 years), and the TwinsUK study as replication, with 724 female participants. Targeted metabolomics of fasting serum samples quantified 131 metabolites by FIA-MS/MS. Among these, 71/34 metabolites were significantly associated with age in women/men (BMI adjusted). We further identified a set of 13 independent metabolites in women (with P values ranging from 4.6 × 10−04 to 7.8 × 10−42, αcorr = 0.004). Eleven of these 13 metabolites were replicated in the TwinsUK study, including seven metabolite concentrations that increased with age (C0, C10:1, C12:1, C18:1, SM C16:1, SM C18:1, and PC aa C28:1), while histidine decreased. These results indicate that metabolic profiles are age dependent and might reflect different aging processes, such as incomplete mitochondrial fatty acid oxidation. The use of metabolomics will increase our understanding of aging networks and may lead to discoveries that help enhance healthy aging. PMID:22834969

  16. The Age of Human Cerebral Cortex Neurons

    SciTech Connect

    Bhardwaj, R D; Curtis, M A; Spalding, K L; Buchholz, B A; Fink, D; Bjork-Eriksson, T; Nordborg, C; Gage, F H; Druid, H; Eriksson, P S; Frisen, J

    2006-04-06

    The traditional static view of the adult mammalian brain has been challenged by the realization of continuous generation of neurons from stem cells. Based mainly on studies in experimental animals, adult neurogenesis may contribute to recovery after brain insults and decreased neurogenesis has been implicated in the pathogenesis of neurological and psychiatric diseases in man. The extent of neurogenesis in the adult human brain has, however, been difficult to establish. We have taken advantage of the integration of {sup 14}C, generated by nuclear bomb tests during the Cold War, in DNA to establish the age of neurons in the major areas of the human cerebral cortex. Together with the analysis of the cortex from patients who received BrdU, which integrates in the DNA of dividing cells, our results demonstrate that whereas non-neuronal cells turn over, neurons in the human cerebral cortex are not generated postnatally at detectable levels, but are as old as the individual.

  17. Human Genome Program Report. Part 1, Overview and Progress

    DOE R&D Accomplishments Database

    1997-11-01

    This report contains Part 1 of a two-part report to reflect research and progress in the U.S. Department of Energy Human Genome Program from 1994 through 1996, with specified updates made just before publication. Part 1 consists of the program overview and report on progress.

  18. Human genome program report. Part 1, overview and progress

    SciTech Connect

    1997-11-01

    This report contains Part 1 of a two-part report to reflect research and progress in the U.S. Department of Energy Human Genome Program from 1994 through 1996, with specified updates made just before publication. Part 1 consists of the program overview and report on progress.

  19. Bitter Taste Receptor Polymorphisms and Human Aging

    PubMed Central

    Carrai, Maura; Crocco, Paolina; Montesanto, Alberto; Canzian, Federico; Rose, Giuseppina; Rizzato, Cosmeri

    2012-01-01

    Several studies have shown that genetic factors account for 25% of the variation in human life span. On the basis of published molecular, genetic and epidemiological data, we hypothesized that genetic polymorphisms of taste receptors, which modulate food preferences but are also expressed in a number of organs and regulate food absorption processing and metabolism, could modulate the aging process. Using a tagging approach, we investigated the possible associations between longevity and the common genetic variation at the three bitter taste receptor gene clusters on chromosomes 5, 7 and 12 in a population of 941 individuals ranging in age from 20 to 106 years from the South of Italy. We found that one polymorphism, rs978739, situated 212 bp upstream of the TAS2R16 gene, shows a statistically significant association (p = 0.001) with longevity. In particular, the frequency of A/A homozygotes increases gradually from 35% in subjects aged 20 to 70 up to 55% in centenarians. These data provide suggestive evidence on the possible correlation between human longevity and taste genetics. PMID:23133589

  20. Epigenetic Mechanisms of the Aging Human Retina.

    PubMed

    Pennington, Katie L; DeAngelis, Margaret M

    2015-01-01

    Degenerative retinal diseases, such as glaucoma, age-related macular degeneration, and diabetic retinopathy, have complex etiologies with environmental, genetic, and epigenetic contributions to disease pathology. Much effort has gone into elucidating both the genetic and the environmental risk factors for these retinal diseases. However, little is known about how these genetic and environmental risk factors bring about molecular changes that lead to pathology. Epigenetic mechanisms have received extensive attention of late for their promise of bridging the gap between environmental exposures and disease development via their influence on gene expression. Recent studies have identified epigenetic changes that associate with the incidence and/or progression of each of these retinal diseases. Therefore, these epigenetic modifications may be involved in the underlying pathological mechanisms leading to blindness. Further genome-wide epigenetic studies that incorporate well-characterized tissue samples, consider challenges similar to those relevant to gene expression studies, and combine the genome-wide epigenetic data with genome-wide genetic and expression data to identify additional potentially causative agents of disease are needed. Such studies will allow researchers to create much-needed therapeutics to prevent and/or intervene in disease progression. Improved therapeutics will greatly enhance the quality of life and reduce the burden of disease management for millions of patients living with these potentially blinding conditions.

  1. Epigenetic Mechanisms of the Aging Human Retina

    PubMed Central

    Pennington, Katie L.; DeAngelis, Margaret M.

    2015-01-01

    Degenerative retinal diseases, such as glaucoma, age-related macular degeneration, and diabetic retinopathy, have complex etiologies with environmental, genetic, and epigenetic contributions to disease pathology. Much effort has gone into elucidating both the genetic and the environmental risk factors for these retinal diseases. However, little is known about how these genetic and environmental risk factors bring about molecular changes that lead to pathology. Epigenetic mechanisms have received extensive attention of late for their promise of bridging the gap between environmental exposures and disease development via their influence on gene expression. Recent studies have identified epigenetic changes that associate with the incidence and/or progression of each of these retinal diseases. Therefore, these epigenetic modifications may be involved in the underlying pathological mechanisms leading to blindness. Further genome-wide epigenetic studies that incorporate well-characterized tissue samples, consider challenges similar to those relevant to gene expression studies, and combine the genome-wide epigenetic data with genome-wide genetic and expression data to identify additional potentially causative agents of disease are needed. Such studies will allow researchers to create much-needed therapeutics to prevent and/or intervene in disease progression. Improved therapeutics will greatly enhance the quality of life and reduce the burden of disease management for millions of patients living with these potentially blinding conditions. PMID:26966390

  2. Retaining an aging nurse workforce: perceptions of human resource practices.

    PubMed

    Palumbo, Mary Val; McIntosh, Barbara; Rambur, Betty; Naud, Shelly

    2009-01-01

    The expected retirement of the largest cohort of nurses will push the RN workforce below projected need by 2020. The challenges of managing a nursing workforce with the majority of nurses over 45 years of age are now necessitating attention to polices for recruitment and retention of older nurses, particularly in rural areas. This convenience sample study employed a mailed survey to investigate perceptions of nurses in 12 institutions (four hospitals, seven home health agencies, and one nursing home serving a small rural state). The goal was to explore rural RNs' perceptions of intent to stay in their current position, with their organization, and employment as a nurse; organizational and unit-level culture regarding older nurses in the workplace; importance of specific human resource practices/policies to their own intention to stay; and extent to which these human resource practices/policies are currently done. The results indicate that although there are similarities across age cohorts, important differences exist that can be addressed to create career-span sensitive policies and practices. This study provides an indicator of progress or lack of progress in addressing older nurse recruitment and retention, and also offers guidance for differentiating policies and practices for younger and older nurses.

  3. Aging attenuates the vestibulosympathetic reflex in humans

    NASA Technical Reports Server (NTRS)

    Ray, Chester A.; Monahan, Kevin D.

    2002-01-01

    BACKGROUND: The vestibular system contributes to sympathetic activation by engagement of the otolith organs. However, there is a significant loss of vestibular function with aging. Therefore, the purpose of the present study was to determine if young and older individuals differ in their cardiovascular and sympathetic responses to otolithic stimulation (ie, head-down rotation, HDR). We hypothesized that responses to otolithic stimulation would be attenuated in older adults because of morphological and physiological alterations that occur in the vestibular system with aging. METHODS AND RESULTS: Arterial blood pressure, heart rate, muscle sympathetic nerve activity (MSNA), and head rotation were measured during HDR in 11 young (26 +/- 1 years) and 11 older (64 +/- 1 years) subjects in the prone posture. Five older subjects performed head rotation (chin to chest) in the lateral decubitus position, which simulates HDR but does not alter afferent inputs from the vestibular system. MSNA responses to HDR were significantly attenuated in older as compared with young subjects (P<0.01). MSNA increased in the older subjects by only 12 +/- 5% as compared with 85 +/- 16% in the young. Furthermore, HDR elicited significant reductions in mean arterial blood pressure in older (Delta-6 +/- 1 mm Hg; P<0.01) but not young subjects (Delta1 +/- 1 mm Hg). In contrast to HDR, head rotation performed in the lateral decubitus position did not elicit hypotension. MSNA responses to baroreceptor unloading and the cold pressor test were not different between the age groups. CONCLUSIONS: These data indicate that aging attenuates the vestibulosympathetic reflex in humans and may contribute to the increased prevalence of orthostatic hypotension with age.

  4. Cumulative knowledge and progress in human factors.

    PubMed

    Proctor, Robert W; Vu, Kim-Phuong L

    2010-01-01

    This review provides a cumulative perspective on current human factors research by first briefly acknowledging previous Annual Review articles. We show that several recent conceptual advances are an outgrowth of the information-processing approach adopted by the field and present several areas of current research that are built directly on prior work. Topic areas that provide fundamental tools for human factors analyses are summarized, and several current application areas are reviewed. We end by considering alternatives to the information-processing approach that have been proposed and placing those alternatives in context. We argue that the information-processing language provides the foundation that has enabled much of the growth in human factors. This growth reflects a cumulative development of concepts and methods that continues today.

  5. Dietary boron: progress in establishing essential roles in human physiology.

    PubMed

    Hunt, Curtiss D

    2012-06-01

    This review summarizes the progress made in establishing essential roles for boron in human physiology and assesses that progress in view of criteria for essentiality of elements. The evidence to date suggests that humans and at least some higher animals may use boron to support normal biological functions. These include roles in calcium metabolism, bone growth and maintenance, insulin metabolism, and completion of the life cycle. The biochemical mechanisms responsible for these effects are poorly understood but the nature of boron biochemistry suggests further characterization of the cell signaling molecules capable of complexing with boron. Such characterization may provide insights into the biochemical function(s) of boron in humans.

  6. Melatonin and aging: prospects for human treatment.

    PubMed

    Bubenik, G A; Konturek, S J

    2011-02-01

    Human life span, with or without modern medicine is around 85-95 years. All living creatures have their inner clock that measures their daily (circadian) and their seasonal (circannual) time. These time changes are mediated by the alteration of levels of melatonin, an evolutionary ancient hormone, which is produced in many body tissues, including the pineal gland, retina and the gastrointestinal tract (GIT). Light is blocking the production of melatonin in the pineal gland, darkness is stimulating it. So, the diurnal changes of light intensity of melatonin, provide a "daily clock" and the seasonal changes provide a "seasonal clock". Finally, the reduction of melatonin observed with aging, may indicate the presence of an "age clock". Melatonin is a strong antioxidant (often it is called scavenger of free radicals), which protects the body from the effects of noxious compounds. Therefore it was hypothesized that the reduction of melatonin levels with age contributes to the aging process. So far, the only remedy to extend the life span was a 40% reduction in caloric intake, which prolonged the life in mice, rats, dogs and monkeys by 30-50%. A large group of people imitate these experiments performed on animals, but the results of these experiments will not be known for several decades. How is being hungry prolonging the life span? There is a connection between caloric reduction and melatonin levels in GIT. Several experiments indicate that fasting in animals substantially increased their production of GIT melatonin. Therefore, instead of being permanently hungry, a prolongation of human life could be achieved by a replacement melatonin therapy. A daily intake of melatonin before bed time might achieve the same effect as fasting e.g. an increase of body melatonin levels, which will protect the individual from the ravages of old age. That includes Parkinson's disease and Alzheimer's disease. There is a large group of people taking melatonin daily who believe that

  7. Modern human origins: progress and prospects.

    PubMed Central

    Stringer, Chris

    2002-01-01

    The question of the mode of origin of modern humans (Homo sapiens) has dominated palaeoanthropological debate over the last decade. This review discusses the main models proposed to explain modern human origins, and examines relevant fossil evidence from Eurasia, Africa and Australasia. Archaeological and genetic data are also discussed, as well as problems with the concept of 'modernity' itself. It is concluded that a recent African origin can be supported for H. sapiens, morphologically, behaviourally and genetically, but that more evidence will be needed, both from Africa and elsewhere, before an absolute African origin for our species and its behavioural characteristics can be established and explained. PMID:12028792

  8. Progress in Human Nutrition, Volume 1.

    ERIC Educational Resources Information Center

    Margen, Sheldon, Ed.

    In view of the international character of nutrition and interrelationships and meaning of food to all people, this annual series of open-ended books has been started to direct attention to the aspects of human nutrition in regard to the quality of life. It is believed the study of the action nutrients, their interrelationships, and their ingestion…

  9. Mitochondrial dysfunction in aging: Much progress but many unresolved questions

    PubMed Central

    Payne, Brendan A.I.; Chinnery, Patrick F.

    2015-01-01

    The free radical theory of aging is almost 60 years old. As mitochondria are the principle source of intracellular reactive oxygen species (ROS), this hypothesis suggested a central role for the mitochondrion in normal mammalian aging. In recent years, however, much work has questioned the importance of mitochondrial ROS in driving aging. Conversely new evidence points to other facets of mitochondrial dysfunction which may nevertheless suggest the mitochondrion retains a critical role at the center of a complex web of processes leading to cellular and organismal aging. PMID:26050973

  10. The aging human recipient of transfusion products.

    PubMed

    Nydegger, Urs E; Luginbühl, Martin; Risch, Martin

    2015-06-01

    In this review the different mechanisms of aging and frailty such as DNA defects due to impaired DNA repair, inflammatory processes, disturbances of oxidative phosphorylation are discussed together with mechanisms of cell repair. Components of blood plasma, such as the growth-differentiation protein GDF11, were shown to enhance neurogenesis and to improve the vasculature in the animal cortex and to rejuvenate muscle tissue. Advances in laboratory assays allow to identify plasma proteins that may affect tissue regeneration. This new knowledge from animal research might affect transfusion practice in geriatric patients in the future. Provided it can be translated and confirmed in human research, blood products might no longer be considered only as oxygen carriers or drugs to improve hemostasis. In the present time blood transfusion (RBCs, plasma or platelets) should be directed by differentiated guidelines considering not only cut-off values of hemoglobin, platelet count or coagulation but also old age-specific biologic variation, comorbidities and the clinical context e.g. of bleeding.

  11. The role of calcium in human aging.

    PubMed

    Beto, Judith A

    2015-01-01

    Calcium is an essential nutrient that is necessary for many functions in human health. Calcium is the most abundant mineral in the body with 99% found in teeth and bone. Only 1% is found in serum. The serum calcium level is tightly monitored to remain within normal range by a complex metabolic process. Calcium metabolism involves other nutrients including protein, vitamin D, and phosphorus. Bone formation and maintenance is a lifelong process. Early attention to strong bones in childhood and adulthood will provide more stable bone mass during the aging years. Research has shown that adequate calcium intake can reduce the risk of fractures, osteoporosis, and diabetes in some populations. The dietary requirements of calcium and other collaborative nutrients vary slightly around the world. Lactose intolerance due to lactase deficiency is a common cause of low calcium intake. Strategies will be discussed for addressing this potential barrier to adequate intake. The purpose of this narrative review is a) to examine the role of calcium in human health, b) to compare nutrient requirements for calcium across lifecycle groups and global populations, c) to review relationships between calcium intake, chronic disease risk, and fractures, and d) to discuss strategies to address diet deficiencies and lactose intolerance.

  12. The Role of Calcium in Human Aging

    PubMed Central

    2015-01-01

    Calcium is an essential nutrient that is necessary for many functions in human health. Calcium is the most abundant mineral in the body with 99% found in teeth and bone. Only 1% is found in serum. The serum calcium level is tightly monitored to remain within normal range by a complex metabolic process. Calcium metabolism involves other nutrients including protein, vitamin D, and phosphorus. Bone formation and maintenance is a lifelong process. Early attention to strong bones in childhood and adulthood will provide more stable bone mass during the aging years. Research has shown that adequate calcium intake can reduce the risk of fractures, osteoporosis, and diabetes in some populations. The dietary requirements of calcium and other collaborative nutrients vary slightly around the world. Lactose intolerance due to lactase deficiency is a common cause of low calcium intake. Strategies will be discussed for addressing this potential barrier to adequate intake. The purpose of this narrative review is a) to examine the role of calcium in human health, b) to compare nutrient requirements for calcium across lifecycle groups and global populations, c) to review relationships between calcium intake, chronic disease risk, and fractures, and d) to discuss strategies to address diet deficiencies and lactose intolerance. PMID:25713787

  13. Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging: A Mini-Review.

    PubMed

    Quan, Taihao; Fisher, Gary J

    2015-01-01

    Human skin is largely composed of a collagen-rich connective tissue, which provides structural and functional support. The collagen-rich connective tissue is produced, organized, and maintained by dermal fibroblasts. During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of collagen fibrils impairs skin structure and function and creates a tissue microenvironment that promotes age-related skin diseases, such as delayed wound healing and skin cancer development. This mini-review describes cellular mechanisms that give rise to self-perpetuating, collagen fibril fragmentation that creates an age-associated dermal microenvironment, which contributes to decline of human skin function.

  14. Face Verification across Age Progression using Discriminative Methods

    DTIC Science & Technology

    2008-01-01

    Under the MURI Grant N00014-08-10638. REFERENCES [1] “Face and gesture recognition working group,” 2000. [Online]. Available: http://www...Conference on Face & Gesture Recognition (FG), 1998, pp. 30–35. [24] A. Montillo and H. Ling, “Age regression from faces using random forests,” in IEEE...aging model.” in International Conference on Face & Gesture Recognition (FG), 2008. [26] E. Patterson, A. Sethuram, M. Albert, K. Ricanek Jr., and M

  15. The anorexia of aging in humans.

    PubMed

    Hays, Nicholas P; Roberts, Susan B

    2006-06-30

    Energy intake is reduced in older individuals, with several lines of evidence suggesting that both physiological impairment of food intake regulation and non-physiological mechanisms are important. Non-physiological causes of the anorexia of aging include social (e.g. poverty, isolation), psychological (e.g. depression, dementia), medical (e.g. edentulism, dysphagia), and pharmacological factors. Physiological factors include changes in taste and smell, diminished sensory-specific satiety, delayed gastric emptying, altered digestion-related hormone secretion and hormonal responsiveness, as well as food intake-related regulatory impairments for which specific mechanisms remain largely unknown. Studies in healthy elderly individuals have shown that men who consume diets over several weeks providing either too few or too many calories relative to dietary energy needs subsequently do not compensate for the resulting energy deficit or surplus when provided an ad libitum diet. Healthy elders have also been shown to be less hungry at meal initiation and to become more rapidly satiated during a standard meal compared to younger adults. Studies in animal models are required to investigate potential mechanisms underlying these observations, while human studies should focus on examining the potential consequences of this phenomenon and practical therapeutic strategies for the maintenance of appropriate energy intake with increasing age. In light of this need, we have recently demonstrated that low reported hunger assessed using a simple questionnaire predicts unintentional weight loss in a sample of healthy older women, and thus may provide a clinically useful tool for identifying older individuals at risk for undesirable weight change and therefore at high priority for intervention.

  16. Human Growth Hormone (HGH): Does It Slow Aging?

    MedlinePlus

    Healthy Lifestyle Healthy aging Human growth hormone is described by some as the key to slowing the aging ... about proven ways to improve your health. Remember, healthy lifestyle choices — such as eating a healthy diet and ...

  17. Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection.

    PubMed

    Blackburn, Elizabeth H; Epel, Elissa S; Lin, Jue

    2015-12-04

    Telomeres are the protective end-complexes at the termini of eukaryotic chromosomes. Telomere attrition can lead to potentially maladaptive cellular changes, block cell division, and interfere with tissue replenishment. Recent advances in the understanding of human disease processes have clarified the roles of telomere biology, especially in diseases of human aging and in some aging-related processes. Greater overall telomere attrition predicts mortality and aging-related diseases in inherited telomere syndrome patients, and also in general human cohorts. However, genetically caused variations in telomere maintenance either raise or lower risks and progression of cancers, in a highly cancer type-specific fashion. Telomere maintenance is determined by genetic factors and is also cumulatively shaped by nongenetic influences throughout human life; both can interact. These and other recent findings highlight both causal and potentiating roles for telomere attrition in human diseases.

  18. Exposure to Chlamydia pneumoniae infection and progression of age-related macular degeneration.

    PubMed

    Robman, Luba; Mahdi, Olaimatu; McCarty, Catherine; Dimitrov, Peter; Tikellis, Gabriella; McNeil, John; Byrne, Gerald; Taylor, Hugh; Guymer, Robyn

    2005-06-01

    Recent studies have found an association between exposure to Chlamydia pneumoniae infection and risk of age-related macular degeneration (AMD). To assess a potential risk of AMD progression posed by exposure to C. pneumoniae, the authors reexamined Australian residents in 2001-2002 who were aged 51-89 years with early AMD at baseline (1992-1995). Examination included macular photography and an enzyme-linked immunosorbent assay to determine antibody titers to the elementary bodies from C. pneumoniae AR39. AMD progression was assessed quantitatively, using both coarse and fine progression steps following an international classification for AMD grading, and also qualitatively, by side-by-side comparison of baseline and follow-up macular photographs. Serologic data were available for 246 of 254 (97%) subjects. AMD progression was associated with a higher antibody titer. After adjustment for age, smoking, family history of AMD, history of cardiovascular diseases, and source study, the subjects in the upper tertiles of antibody titers were 2.1 (95% confidence interval: 0.92, 4.69), 2.6 (95% confidence interval: 1.24, 5.41), and 3.0 (95% confidence interval: 1.46, 6.37) times more at risk of progression than those in the lowest tertile, using three definitions of progression, respectively. The fact that seroreactivity to C. pneumoniae was independently associated with the risk of AMD progression suggests that C. pneumoniae infection may be an additional risk factor for AMD progression.

  19. Old age at diagnosis increases risk of tumor progression in nasopharyngeal cancer

    PubMed Central

    He, Yao-Xuan; Chen, Xiao-Di; Zhang, Guo-Ye; Li, Zhi-Kun; Hong, Jing; Xie, Dan; Cai, Mu-Yan

    2016-01-01

    Age at diagnosis has been found to be a prognostic factor of outcomes in various cancers. However, the effect of age at diagnosis on nasopharyngeal cancer (NPC) progression has not been explored. We retrospectively evaluated the relationship between age and disease progression in 3,153 NPC patients who underwent radiotherapy, chemotherapy, or chemoradiotherapy between 2007 and 2009. Patients were randomly assigned to either a testing cohort or a validation cohort by computer-generated random assignment. X-tile plots determined the optimal cut-point of age based on survival status to be ≤61 vs. >61 years. Further correlation analysis showed that age >61 years was significantly correlated with the tumor progression and therapeutic regimen in both testing and validation cohorts (P <0.05). In the present study, we observed that older age (>61 years) was a strong and independent predictor of poor disease-free survival (DFS) and cancer-specific survival (CSS), in both univariate and multivariate analyses. Age was also found to be a significant prognostic predictor as well (P <0.05) when evaluating patients with the same disease stage. ROC analysis confirmed the predictive value of age on NPC-specific survival in both cohorts (P <0.001) and suggested that age may improve the ability to discriminate outcomes in NPCs, especially regarding tumor progression. In conclusion, our study suggests that older age at NPC diagnosis is associated with a higher incidence of tumor progression and cancer-specific mortality. Age is a strong and independent predictor of poor outcomes and may allow for more tailored therapeutic decision-making and individualized patient counseling. PMID:27463012

  20. Olfactory phenotypic expression unveils human aging

    PubMed Central

    Mazzatenta, Andrea; Cellerino, Alessandro; Origlia, Nicola; Barloscio, Davide; Sartucci, Ferdinando; Giulio, Camillo Di; Domenici, Luciano

    2016-01-01

    The mechanism of the natural aging of olfaction and its declinein the absence of any overt disease conditions remains unclear. Here, we investigated this mechanism through measurement of one of the parameters of olfactory function, the absolute threshold, in a healthy population from childhood to old age. The absolute olfactory threshold data were collected from an Italian observational study with 622 participants aged 5-105 years. A subjective testing procedure of constant stimuli was used, which was also compared to the ‘staircase’ method, with the calculation of the reliability. The n-butanol stimulus was used as an ascending series of nine molar concentrations that were monitored using an electronic nose. The data were analyzed using nonparametric statistics because of the multimodal distribution. We show that the age-related variations in the absolute olfactory threshold are not continuous; instead, there are multiple olfactory phenotypes. Three distinct age-related phenotypes were defined, termed as ‘juvenile’, ‘mature’ and ‘elder’. The frequency of these three phenotypes depends on age. Our data suggest that the sense of smell does not decrease linearly with aging. Our findings provide the basis for further understanding of olfactory loss as an anticipatory sign of aging and neurodegenerative processes. PMID:27027240

  1. Early Characteristics of Children with ASD Who Demonstrate Optimal Progress Between Age Two and Four.

    PubMed

    Moulton, Emily; Barton, Marianne; Robins, Diana L; Abrams, Danielle N; Fein, Deborah

    2016-06-01

    Although for many children, Autism Spectrum Disorder (ASD) is a lifelong disability, a subset of children with ASD lose their diagnosis and show typical cognitive and adaptive abilities. The ages at which this transition can occur is not known, but it sometimes occurs quite early. Participants in the current study were 207 children with an ASD at age two who were reevaluated at age four. Eighty-three percent retained an ASD diagnosis at reevaluation and 9 % showed "optimal progress": clear ASD at age two but not at age four, and average cognition, language, communication and social skills at age four. Early child-level factors predicted optimal progress: diagnosis of PDD-NOS, fewer repetitive behaviors, less severe symptomatology and stronger adaptive skills.

  2. Reliability of the Raven Colored Progressive Matrices Test: Age and Ethnic Group Comparisons.

    ERIC Educational Resources Information Center

    Carlson, Jerry S.; Jensen, C. Mark

    1981-01-01

    Reliabilities for the Raven Colored Progressive Matrices Test (CPM) are reported for three age groups (ages 5 1/2- 6 1/2, 6 1/2-7 1/2, and 7 1/2-8 1/2 years) and three ethnic groups (Anglo, Black, and Hispanic). Results indicate CPM is not equally reliable for all age groups, but appears equally reliable for the three ethnic groups. (Author)

  3. Failure of Urological Implants in Spinal Cord Injury Patients due to Infection, Malfunction, and Implants Becoming Obsolete due to Medical Progress and Age-Related Changes in Human Body Making Implant Futile: Report of Three Cases.

    PubMed

    Vaidyanathan, Subramanian; Soni, Bakul; Singh, Gurpreet; Hughes, Peter; Selmi, Fahed; Mansour, Paul

    2013-01-01

    Any new clinical data, whether positive or negative, generated about a medical device should be published because health professionals should know which devices do not work, as well as those which do. We report three spinal cord injury patients in whom urological implants failed to work. In the first, paraplegic, patient, a sacral anterior root stimulator failed to produce erection, and a drug delivery system for intracavernosal administration of vasoactive drugs was therefore implanted; however, this implant never functioned (and, furthermore, such penile drug delivery systems to produce erection had effectively become obsolete following the advent of phosphodiesterase type 5 inhibitors). Subsequently, the sacral anterior root stimulator developed a malfunction and the patient therefore learned to perform self-catheterisation. In the second patient, also paraplegic, an artificial urinary sphincter was implanted but the patient developed a postoperative sacral pressure sore. Eight months later, a suprapubic cystostomy was performed as urethral catheterisation was very difficult. The pressure sore had not healed completely even after five years. In the third case, a sacral anterior root stimulator was implanted in a tetraplegic patient in whom, after five years, a penile sheath could not be fitted because of penile retraction. This patient was therefore established on urethral catheter drainage. Later, infection with Staphylococcus aureus around the receiver block necessitated its removal. In conclusion, spinal cord injury patients are at risk of developing pressure sores, wound infections, malfunction of implants, and the inability to use implants because of age-related changes, as well as running the risk of their implants becoming obsolete due to advances in medicine. Some surgical procedures such as dorsal rhizotomy are irreversible. Alternative treatments such as intermittent catheterisations may be less damaging than bladder stimulator in the long term.

  4. Molecular aging and rejuvenation of human muscle stem cells

    PubMed Central

    Carlson, Morgan E; Suetta, Charlotte; Conboy, Michael J; Aagaard, Per; Mackey, Abigail; Kjaer, Michael; Conboy, Irina

    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-β)/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 understanding, combined with data that human satellite cells remain intrinsically young, introduced novel therapeutic targets. Indeed, activation of MAPK/Notch restored ‘youthful’ myogenic responses to satellite cells from 70-year-old humans, rendering them similar to cells from 20-year-old humans. These findings strongly suggest that aging of human muscle maintenance and repair can be reversed by ‘youthful’ calibration of specific molecular pathways. PMID:20049743

  5. Myths of Human Sexuality in the Aging.

    ERIC Educational Resources Information Center

    Andrus, Charles E.

    Human sexuality is discussed in terms of misconceptions about its function and the changing sexual needs of older adults. A review of history indicates that human sexuality has traditionally been connected with ideas of purity and strict importance of procreation. Judaeo-Christian ethics and the doctrine of Saint Augustine illustrate these…

  6. Genetic evidence for common pathways in human age-related diseases

    PubMed Central

    Johnson, Simon C; Dong, Xiao; Vijg, Jan; Suh, Yousin

    2015-01-01

    Aging is the single largest risk factor for chronic disease. Studies in model organisms have identified conserved pathways that modulate aging rate and the onset and progression of multiple age-related diseases, suggesting that common pathways of aging may influence age-related diseases in humans as well. To determine whether there is genetic evidence supporting the notion of common pathways underlying age-related diseases, we analyzed the genes and pathways found to be associated with five major categories of age-related disease using a total of 410 genomewide association studies (GWAS). While only a small number of genes are shared among all five disease categories, those found in at least three of the five major age-related disease categories are highly enriched for apoliprotein metabolism genes. We found that a more substantial number of gene ontology (GO) terms are shared among the 5 age-related disease categories and shared GO terms include canonical aging pathways identified in model organisms, such as nutrient-sensing signaling, translation, proteostasis, stress responses, and genome maintenance. Taking advantage of the vast amount of genetic data from the GWAS, our findings provide the first direct evidence that conserved pathways of aging simultaneously influence multiple age-related diseases in humans as has been demonstrated in model organisms. PMID:26077337

  7. Biomimetic remineralization as a progressive dehydration mechanism of collagen matrices – implications in the aging of resin-dentin bonds

    PubMed Central

    Kim, Young Kyung; Mai, Sui; Mazzoni, Annalisa; Liu, Yan; Tezvergil-Mutluay, Arzu; Takahashi, Kei; Zhang, Kai; Pashley, David H.; Tay, Franklin R.

    2010-01-01

    Biomineralization is a dehydration process in which water from the intrafibrillar compartments of collagen fibrils are progressively replaced by apatites. As water is an important element that precipitates the lack of durability of resin-dentin bonds, this study examined the use of a biomimetic remineralization strategy as a progressive dehydration mechanism for preserving joint integrity and maintaining adhesive strength after aging. Human dentin surfaces were bonded with dentin adhesives, restored with resin composites and sectioned into sticks containing the adhesive joint. Experimental specimens were aged in a biomimetic analog-containing remineralizing medium and control specimens in simulated body fluid for up to 12 months. Specimens retrieved from the designated periods were examined by transmission electron microscopy for manifestation of water-rich regions using a silver tracer and for collagen degradation within the adhesive joints. Tensile testing was performed to determine the potential loss of bond integrity after aging. Control specimens exhibited severe collagen degradation within the adhesive joint after aging. Remineralized specimens exhibited progressive dehydration as manifested by silver tracer reduction and partial remineralization of water-filled micro-channels within the adhesive joint, as well as intrafibrillar remineralization of collagen fibrils that were demineralized initially as part of the bonding procedure. Biomimetic remineralization as a progressive dehydration mechanism of water-rich, resin-sparse collagen matrices enables those adhesive joints to resist degradation over the 12-month aging period, as verified by the conservation of their tensile bond strengths. The ability of the proof-of-concept biomimetic remineralization strategy to prevent bond degradation warrants further development of clinically-relevant delivery systems. PMID:20304110

  8. Oxidative Stress in Aging Human Skin

    PubMed Central

    Rinnerthaler, Mark; Bischof, Johannes; Streubel, Maria Karolin; Trost, Andrea; Richter, Klaus

    2015-01-01

    Oxidative stress in skin plays a major role in the aging process. This is true for intrinsic aging and even more for extrinsic aging. Although the results are quite different in dermis and epidermis, extrinsic aging is driven to a large extent by oxidative stress caused by UV irradiation. In this review the overall effects of oxidative stress are discussed as well as the sources of ROS including the mitochondrial ETC, peroxisomal and ER localized proteins, the Fenton reaction, and such enzymes as cyclooxygenases, lipoxygenases, xanthine oxidases, and NADPH oxidases. Furthermore, the defense mechanisms against oxidative stress ranging from enzymes like superoxide dismutases, catalases, peroxiredoxins, and GSH peroxidases to organic compounds such as L-ascorbate, α-tocopherol, beta-carotene, uric acid, CoQ10, and glutathione are described in more detail. In addition the oxidative stress induced modifications caused to proteins, lipids and DNA are discussed. Finally age-related changes of the skin are also a topic of this review. They include a disruption of the epidermal calcium gradient in old skin with an accompanying change in the composition of the cornified envelope. This modified cornified envelope also leads to an altered anti-oxidative capacity and a reduced barrier function of the epidermis. PMID:25906193

  9. Ageing and recurrent episodes of neuroinflammation promote progressive experimental autoimmune encephalomyelitis in Biozzi ABH mice.

    PubMed

    Peferoen, Laura A N; Breur, Marjolein; van de Berg, Sarah; Peferoen-Baert, Regina; Boddeke, Erik H W G M; van der Valk, Paul; Pryce, Gareth; van Noort, Johannes M; Baker, David; Amor, Sandra

    2016-10-01

    Current therapies for multiple sclerosis (MS) reduce the frequency of relapses by modulating adaptive immune responses but fail to limit the irreversible neurodegeneration driving progressive disability. Experimental autoimmune encephalomyelitis (EAE) in Biozzi ABH mice recapitulates clinical features of MS including relapsing-remitting episodes and secondary-progressive disability. To address the contribution of recurrent inflammatory events and ageing as factors that amplify progressive neurological disease, we examined EAE in 8- to 12-week-old and 12-month-old ABH mice. Compared with the relapsing-remitting (RREAE) and secondary progressive (SPEAE) EAE observed in young mice, old mice developed progressive disease from onset (PEAE) associated with pronounced axonal damage and increased numbers of CD3(+) T cells and microglia/macrophages, but not B cells. Whereas the clinical neurological features of PEAE and SPEAE were comparable, the pathology was distinct. SPEAE was associated with significantly reduced perivascular infiltrates and T-cell numbers in the central nervous system (CNS) compared with PEAE and the acute phase of RREAE. In contrast to perivascular infiltrates that declined during progression from RREAE into SPEAE, the numbers of microglia clusters remained constant. Similar to what is observed during MS, the microglia clusters emerging during EAE were associated with axonal damage and oligodendrocytes expressing heat-shock protein B5, but not lymphocytes. Taken together, our data reveal that the course of EAE is dependent on the age of the mice. Younger mice show a relapsing-remitting phase followed by progressive disease, whereas old mice immediately show progression. This indicates that recurrent episodes of inflammation in the CNS, as well as age, contribute to progressive neurological disease.

  10. [Visual pattern analysis and reasoning: Ravens' Coloured Progressive Matrices in old-age and very-old-age adults].

    PubMed

    Diesfeldt, H F; Vink, M T

    1989-12-06

    Sixty-five non-demented elderly adults, born between 1895 and 1918 (mean age +/- sd: 80.0 +/- 5.4) were tested with Raven's Coloured Progressive Matrices (CPM). Subjects were recruited from homes for the aged and were rated by the staff as free from any symptoms of dementia or other psychiatric disease. Mean number of years of education was 8.2 (range 5 to 18). CPM scores ranged from 9 to 35 with mean +/- sd of 25.9 +/- 5.9. Subjects who had received more formal education performed better on the CPM (Pearson's r: 0.49). When education was controlled for in the analysis, the correlation between age and performance was attenuated and did not reach statistical significance (Pearson's r: -0.24). Test results appeared to be specific for generations, regardless of age. Mean performance in this sample was significantly higher than less recently published norms suggest. Analysis of item content revealed that the CPM consists of three main types of problems: two of a predominantly visuospatial type (12 items of simple continuous pattern-completion and 15 concrete items showing progressive changes in one or two directions) and 9 items of an abstract reasoning type. The concrete visuospatial items appear very useful in the assessment of visuoperceptive dysfunction, as for example in visual apperceptive agnosia. The abstract matrices were very difficult for most of our elderly subjects, so that these items cannot be used to detect deviations from normal old age.

  11. Aging of the Human Vestibular System

    PubMed Central

    Zalewski, Christopher K.

    2015-01-01

    Aging affects every sensory system in the body, including the vestibular system. Although its impact is often difficult to quantify, the deleterious impact of aging on the vestibular system is serious both medically and economically. The deterioration of the vestibular sensory end organs has been known since the 1970s; however, the measurable impact from these anatomical changes remains elusive. Tests of vestibular function either fall short in their ability to quantify such anatomical deterioration, or they are insensitive to the associated physiologic decline and/or central compensatory mechanisms that accompany the vestibular aging process. When compared with healthy younger individuals, a paucity of subtle differences in test results has been reported in the healthy older population, and those differences are often observed only in response to nontraditional and/or more robust stimuli. In addition, the reported differences are often clinically insignificant insomuch that the recorded physiologic responses from the elderly often fall within the wide normative response ranges identified for normal healthy adults. The damaging economic impact of such vestibular sensory decline manifests itself in an exponential increase in geriatric dizziness and a subsequent higher prevalence of injurious falls. An estimated $10 to $20 billion dollar annual cost has been reported to be associated with falls-related injuries and is the sixth leading cause of death in the elderly population, with a 20% mortality rate. With an estimated 115% increase in the geriatric population over 65 years of age by the year 2050, the number of balanced-disordered patients with a declining vestibular system is certain to reach near epidemic proportions. An understanding of the effects of age on the vestibular system is imperative if clinicians are to better manage elderly patients with balance disorders, dizziness, and vestibular disease. PMID:27516717

  12. [Research progress on free radicals in human body].

    PubMed

    Wang, Q B; Xu, F P; Wei, C X; Peng, J; Dong, X D

    2016-08-10

    Free radicals are the intermediates of metabolism, widely exist in the human bodies. Under normal circumstances, the free radicals play an important role in the metabolic process on human body, cell signal pathway, gene regulation, induction of cell proliferation and apoptosis, so as to maintain the normal growth and development of human body and to inhibit the growth of bacteria, virus and cancer. However, when organic lesion occurs affected by external factors or when equilibrium of the free radicals is tipped in the human body, the free radicals will respond integratedly with lipids, protein or nucleic acid which may jeopardize the health of human bodies. This paper summarizes the research progress of the free radicals conducted in recent years, in relations to the perspective of the types, origins, test methods of the free radicals and their relationship with human's health. In addition, the possible mechanisms of environmental pollutants (such as polycyclic aromatic hydrocarbons) mediating oxidative stress and free radicals scavenging in the body were also summarized.

  13. The Association between Maternal Reproductive Age and Progression of Refractive Error in Urban Students in Beijing

    PubMed Central

    Vasudevan, Balamurali; Jin, Zi Bing; Ciuffreda, Kenneth J.; Jhanji, Vishal; Zhou, Hong Jia; Wang, Ning Li; Liang, Yuan Bo

    2015-01-01

    Purpose To investigate the association between maternal reproductive age and their children’ refractive error progression in Chinese urban students. Methods The Beijing Myopia Progression Study was a three-year cohort investigation. Cycloplegic refraction of these students at both baseline and follow-up vision examinations, as well as non-cycloplegic refraction of their parents at baseline, were performed. Student’s refractive change was defined as the cycloplegic spherical equivalent (SE) of the right eye at the final follow-up minus the cycloplegic SE of the right eye at baseline. Results At the final follow-up, 241 students (62.4%) were reexamined. 226 students (58.5%) with completed refractive data, as well as completed parental reproductive age data, were enrolled. The average paternal and maternal age increased from 29.4 years and 27.5 years in 1993–1994 to 32.6 years and 29.2 years in 2003–2004, respectively. In the multivariate analysis, students who were younger (β = 0.08 diopter/year/year, P<0.001), with more myopic refraction at baseline (β = 0.02 diopter/year/diopter, P = 0.01), and with older maternal reproductive age (β = -0.18 diopter/year/decade, P = 0.01), had more myopic refractive change. After stratifying the parental reproductive age into quartile groups, children with older maternal reproductive age (trend test: P = 0.04) had more myopic refractive change, after adjusting for the children's age, baseline refraction, maternal refraction, and near work time. However, no significant association between myopic refractive change and paternal reproductive age was found. Conclusions In this cohort, children with older maternal reproductive age had more myopic refractive change. This new risk factor for myopia progression may partially explain the faster myopic progression found in the Chinese population in recent decades. PMID:26421841

  14. Human microbiota-associated swine: current progress and future opportunities.

    PubMed

    Wang, Mei; Donovan, Sharon M

    2015-01-01

    Gnotobiotic (GN) rodent models have provided insight into the contributions of the gut microbiota to host health and preventing disease. However, rodent models are limited by several important physiological and metabolic differences from humans, and many rodent models do not dependably replicate the clinical manifestations of human diseases. Due to the high degree of similarity in anatomy, physiology, immunology and brain growth, the domestic pig (Sus scrofa) is considered a clinically relevant model to study factors influencing human gastrointestinal, immune, and brain development. Gnotobiotic piglet models have been developed and shown to recapitulate key aspects of GN rodent models. Human microbiota-associated (HMA) piglets have been established using inocula from infants, children, and adults. The gut microbiota of recipient HMA piglets was more similar to that of the human donor than that of conventionally reared piglets harboring a pig microbiota. Moreover, Bifidobacterium and Bacteroides, two predominant bacterial groups of infant gut, were successfully established in the HMA piglets. Thus, the HMA pig model has the potential to be a valuable model for investigating how the gut microbiota composition changes in response to environmental factors, such as age, diet, vaccination, antibiotic use and infection. The HMA also represents a robust model for screening the efficacy of pre- and probiotic interventions. Lastly, HMA piglets can be an ideal model with which to elucidate microbe-host interactions in human health and disease due to the similarities to humans in anatomy, physiology, developmental maturity at birth, and the pathophysiology of many human diseases.

  15. Human Values in a Technological Age.

    ERIC Educational Resources Information Center

    Gorman, Michael

    2001-01-01

    Discusses technology and its effects on society and humans, particularly library and information technology. Highlights include the evolving history of technology; and values related to technology in libraries, including democracy, stewardship, service, intellectual freedom, privacy, literacy and learning, rationalism, and equity of access. (LRW)

  16. T CELL REPLICATIVE SENESCENCE IN HUMAN AGING

    PubMed Central

    Chou, Jennifer P.; Effros, Rita B.

    2013-01-01

    The decline of the immune system appears to be an intractable consequence of aging, leading to increased susceptibility to infections, reduced effectiveness of vaccination and higher incidences of many diseases including osteoporosis and cancer in the elderly. These outcomes can be attributed, at least in part, to a phenomenon known as T cell replicative senescence, a terminal state characterized by dysregulated immune function, loss of the CD28 costimulatory molecule, shortened telomeres and elevated production of pro-inflammatory cytokines. Senescent CD8 T cells, which accumulate in the elderly, have been shown to frequently bear antigen specificity against cytomegalovirus (CMV), suggesting that this common and persistent infection may drive immune senescence and result in functional and phenotypic changes to the T cell repertoire. Senescent T cells have also been identified in patients with certain cancers, autoimmune diseases and chronic infections, such as HIV. This review discusses the in vivo and in vitro evidence for the contribution of CD8 T cell replicative senescence to a plethora of age-related pathologies and a few possible therapeutic avenues to delay or prevent this differentiative end-state in T cells. The age-associated remodeling of the immune system, through accumulation of senescent T cells has far-reaching consequences on the individual and society alike, for the current healthcare system needs to meet the urgent demands of the increasing proportions of the elderly in the US and abroad. PMID:23061726

  17. Immunolocalisation pattern of complex I-V in ageing human retina: Correlation with mitochondrial ultrastructure.

    PubMed

    Nag, Tapas Chandra; Wadhwa, Shashi

    2016-11-01

    Earlier studies reported accumulation of mitochondrial DNA mutations in ageing and age-related macular degeneration. To know about the mitochondrial status with age, we examined immunoreactivity (IR) to markers of mitochondria (anti-mitochondrial antibody and voltage-dependent anion channel-1) and complex I-V (that mediate oxidative phosphorylation, OXPHOS) in donor human retinas (age: 19-94years; N=26; right eyes). In all samples, at all ages, IR to anti-mitochondrial antibody and voltage-dependent anion channel-1 was prominent in photoreceptor cells. Between second and seventh decade of life, strong IR to complex I-V was present in photoreceptors over macular to peripheral retina. With progressive ageing, the photoreceptors showed a decrease in complex I-IR (subunit NDUFB4) at eighth decade, and a weak or absence of IR in 10 retinas between ninth and tenth decade. Patchy IR to complex III and complex IV was detected at different ages. IR to ND1 (complex I) and complex II and V remained unaltered with ageing. Nitrosative stress (evaluated by IR to a nitro-tyrosine antibody) was found in photoreceptors. Superoxide dismutase-2 was found upregulated in photoreceptors with ageing. Mitochondrial ultrastructure was examined in two young retinas with intact complex IR and six aged retinas whose counterparts showed weak to absence of IR. Observations revealed irregular, photoreceptor inner segment mitochondria in aged maculae and mid-peripheral retina between eighth and ninth decade; many cones possessed autophagosomes with damaged mitochondria, indicating age-related alterations. A trend in age-dependent reduction of complex I-IR was evident in aged photoreceptors, whereas patchy complex IV-IR (subunits I and II) was age-independent, suggesting that the former is prone to damage with ageing perhaps due to oxidative stress. These changes in OXPHOS system may influence the energy budget of human photoreceptors, affecting their viability.

  18. Progression of aging in Mexico: the Mexican Health and Aging Study (MHAS) 2012

    PubMed Central

    Wong, Rebeca; Michaels-Obregón, Alejandra; Palloni, Alberto; Gutiérrez-Robledo, Luis Miguel; González-González, César; López-Ortega, Mariana; Téllez-Rojo, Martha María; Mendoza-Alvarado, Laura Rosario

    2015-01-01

    Objective To describe the third wave of the Mexican Health and Aging Study (MHAS), completed in 2012, and present preliminary results. Materials and methods Descriptive analyses by gender and age group of demographic and socioeconomic characteristics, health conditions and health behaviors, as well as social support and life satisfaction measures are presented. In addition, external validations are presented by comparing MHAS 2012 indicators with other national data sources. Results For the panel of older adults in the sample, the rate of health care insurance coverage increased greatly between 2001 and 2012, a significantly higher change in rural compared to urban areas. The results for 2012 are consistent with the previous two waves for the main indicators of health and physical disability prevalence, risk factors, and behaviors. Conclusions The MHAS offers a unique opportunity to study aging in Mexico, as well as to complete cross-national comparisons. The cumulative number of deaths in the cohort should support the study of mortality and its association with health outcomes and behaviors over the life cycle. In addition, the sub-samples of objective markers will enable methodological research on self-reports and associations of biomarkers in old age with similar health outcomes and behaviors. PMID:26172238

  19. Heat waves, aging, and human cardiovascular health.

    PubMed

    Kenney, W Larry; Craighead, Daniel H; Alexander, Lacy M

    2014-10-01

    This brief review is based on a President's Lecture presented at the Annual Meeting of the American College of Sports Medicine in 2013. The purpose of this review was to assess the effects of climate change and consequent increases in environmental heat stress on the aging cardiovascular system. The earth's average global temperature is slowly but consistently increasing, and along with mean temperature changes come increases in heat wave frequency and severity. Extreme passive thermal stress resulting from prolonged elevations in ambient temperature and prolonged physical activity in hot environments creates a high demand on the left ventricle to pump blood to the skin to dissipate heat. Even healthy aging is accompanied by altered cardiovascular function, which limits the extent to which older individuals can maintain stroke volume, increase cardiac output, and increase skin blood flow when exposed to environmental extremes. In the elderly, the increased cardiovascular demand during heat waves is often fatal because of increased strain on an already compromised left ventricle. Not surprisingly, excess deaths during heat waves 1) occur predominantly in older individuals and 2) are overwhelmingly cardiovascular in origin. Increasing frequency and severity of heat waves coupled with a rapidly growing at-risk population dramatically increase the extent of future untoward health outcomes.

  20. Age effects on B cells and humoral immunity in humans

    PubMed Central

    Frasca, Daniela; Diaz, Alain; Romero, Maria; Landin, Ana Marie; Blomberg, Bonnie B

    2010-01-01

    Both humoral and cellular immune responses are impaired in aged individuals, leading to decreased vaccine responses. Although T cell defects occur, defects in B cells play a significant role in age-related humoral immune changes. The ability to undergo class switch recombination (CSR), the enzyme for CSR, AID (activation-induced cytidine deaminase) and the transcription factor E47 are all decreased in aged stimulated B cells. We here present an overview of age-related changes in human B cell markers and functions, and also discuss some controversies in the field of B cell aging. PMID:20728581

  1. RORα and RORγ expression inversely correlates with human melanoma progression

    PubMed Central

    Brożyna, Anna A.; Jóźwicki, Wojciech; Skobowiat, Cezary; Jetten, Anton; Slominski, Andrzej T.

    2016-01-01

    The retinoic acid-related orphan receptors (RORs) regulate several physiological and pathological processes, including immune functions, development and cancer. To study the potential role of RORs in melanoma progression, we analysed RORα and RORγ expression in nevi and primary melanomas and non-lesional skin and metastases in relation to melanoma clinico-pathomorphological features. The expression of RORα and RORγ was lower in melanomas than in nevi and decreased during melanoma progression, with lowest levels found in primary melanomas at stages III and IV and in melanoma metastases. Their expression correlated with pathomorphological pTNM parameters being low in aggressive tumors and being high in tumors showing histological markers of good prognosis. Higher nuclear levels of RORα and RORγ and of cytoplasmic RORγ correlated with significantly longer overall and disease free survival time. Highly pigmented melanomas showed significantly lower level of nuclear RORs. This study shows that human melanoma development and aggressiveness is associated with decreased expression of RORα and RORγ, suggesting that RORs could be important in melanoma progression and host responses against the tumor. Furthermore, it suggests that RORα and RORγ might constitute a novel druggable target in anti-melanoma management using tumor suppressor gene therapy restoring their normal functions. PMID:27542227

  2. CHL1 is involved in human breast tumorigenesis and progression

    SciTech Connect

    He, Li-Hong; Ma, Qin; Shi, Ye-Hui; Ge, Jie; Zhao, Hong-Meng; Li, Shu-Fen; Tong, Zhong-Sheng

    2013-08-23

    Highlights: •CHL1 is down-regulation in breast cancer tissues. •Down-regulation of CHL1 is related to high grade. •Overexpression of CHL1 inhibits breast cancer cell proliferation and invasion in vitro. •CHL1 deficiency induces breast cancer cell proliferation and invasion both in vitro and in vivo. -- Abstract: Neural cell adhesion molecules (CAM) play important roles in the development and regeneration of the nervous system. The L1 family of CAMs is comprised of L1, Close Homolog of L1 (CHL1, L1CAM2), NrCAM, and Neurofascin, which are structurally related trans-membrane proteins in vertebrates. Although the L1CAM has been demonstrated play important role in carcinogenesis and progression, the function of CHL1 in human breast cancer is limited. Here, we found that CHL1 is down-regulated in human breast cancer and related to lower grade. Furthermore, overexpression of CHL1 suppresses proliferation and invasion in MDA-MB-231 cells and knockdown of CHL1 expression results in increased proliferation and invasion in MCF7 cells in vitro. Finally, CHL1 deficiency promotes tumor formation in vivo. Our results may provide a strategy for blocking breast carcinogenesis and progression.

  3. Current progress of DNA vaccine studies in humans.

    PubMed

    Lu, Shan; Wang, Shixia; Grimes-Serrano, Jill M

    2008-03-01

    Despite remarkable progress in the field of DNA vaccine research since its discovery in the early 1990 s, the formal acceptance of this novel technology as a new modality of human vaccines depends on the successful demonstration of its safety and efficacy in advanced clinical trials. Although clinical trials conducted so far have provided overwhelming evidence that DNA vaccines are well tolerated and have an excellent safety profile, the early designs of DNA vaccines failed to demonstrate sufficient immunogenicity in humans. However, studies conducted over the last few years have led to promising results, particularly when DNA vaccines were used in combination with other forms of vaccines. Here, we provide a review of the data from reported DNA vaccine clinical studies with an emphasis on the ability of DNA vaccines to elicit antigen-specific, cell-mediated and antibody responses in humans. The majority of these trials are designed to test candidate vaccines against several major human pathogens and the remaining studies tested the immunogenicity of therapeutic vaccines against cancer.

  4. Involvement of human papillomavirus infections in prostate cancer progression.

    PubMed

    Al Moustafa, Ala-Eddin

    2008-08-01

    High-risk human papillomaviruses (HPVs) are sexually transmitted and have been associated with several human carcinomas especially cervical and colorectal. On the other hand, a small number of studies have examined the presence of high-risk HPV in human prostate cancer tissues. Currently, the presence and role of high-risk HPV infections in prostate carcinogenesis remain unclear because of the limited number of investigations. This raises the question whether high-risk HPV infections play any role in human prostate cancer development. However, other investigators and our group were able to immortalize normal and cancer prostate epithelial cells in vitro by E6/E7 of HPV type 16. In this paper, we propose the hypothesis that normal and cancer prostate epithelial cells are susceptible to persistent HPV infections; therefore, high-risk HPV infections play an important role in the progression of prostate cancer. We believe that an international collaboration of epidemiological studies and more molecular biology investigations are necessary to answer these important questions.

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

    PubMed

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

    2016-01-01

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

  6. Uniquely Human Self-Control Begins at School Age

    ERIC Educational Resources Information Center

    Herrmann, Esther; Misch, Antonia; Hernandez-Lloreda, Victoria; Tomasello, Michael

    2015-01-01

    Human beings have remarkable skills of self-control, but the evolutionary origins of these skills are unknown. Here we compare children at 3 and 6 years of age with one of humans' two nearest relatives, chimpanzees, on a battery of reactivity and self-control tasks. Three-year-old children and chimpanzees were very similar in their abilities to…

  7. Relationship between erythrocyte volume and cell age in humans and baboons. Technical report

    SciTech Connect

    Thompson, C.B.; Galli, R.L.; Melaragno, A.J.; Valeri, C.R.

    1983-03-30

    The relationship of red blood cell size to age during steady-state hematopoiesis has been studied using erythrocytes separated on the basis of size using counterflow centrifugation. The ratio of the age-related enzyme, erythrocyte glutamic oxaloacetic transferase (EGOT), to hemoglobin (Hb) increased progressively through the fractions, suggesting a correlation between erythrocyte volume and age. Reticulocytes, while present in all fractions, were selectively enriched in the larger subpopulations. To verify the biochemical evidence that erythrocytes decrease in volume with aging, in vivo cohort labeling of red blood cells with 59Fe was performed in baboons. A similar relationship of EGOT to Hb was observed to that in the human subpopulations. While a certain amount of erythrocyte volume heterogeneity seems to be present as a result of erythropoeisis, our data support the hypothesis that red blood cells decrease in volume as they age.

  8. Forensic age estimation in human skeletal remains: current concepts and future directions.

    PubMed

    Franklin, Daniel

    2010-01-01

    Skeletal identification has a long tradition in both physical and forensic anthropology. The process generally begins with formulation of a biological profile (osteobiography); specifically, estimation of sex, age, ethnicity and stature. The present paper briefly reviews a selection of the principal methods used for one aspect of the identification process; the estimation of personal age. It is well-documented that variability in the morphological features used to assess age in the human skeleton progressively increases from birth to old age. Thus choice of method is inherently related to whether unidentified remains are those of a juvenile or an adult. This review, therefore, considers methods appropriate for age estimation in both juvenile and adult remains; the former being primarily based on developmental, and the latter degenerative, morphological features. Such a review is timely as new methods are constantly being developed, concurrent with refinements to those already well established in mainstream anthropology.

  9. Epigenetic Age Acceleration Assessed With Human White-Matter Images.

    PubMed

    Hodgson, Karen; Carless, Melanie A; Kulkarni, Hemant; Curran, Joanne E; Sprooten, Emma; Knowles, Emma E; Mathias, Samuel; Göring, Harald Hh; Yao, Nailin; Olvera, Rene L; Fox, Peter T; Almasy, Laura; Duggirala, Ravi; Blangero, John; Glahn, David C

    2017-04-06

    The accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie inter-individual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample (n=628; age=23.28-93.11 years), epigenetic age was estimated using the method developed by S. Horvath (2013). For n=376 individuals, DTI scans were also available. The interrelationship between epigenetic age acceleration and global white matter integrity were investigated with variance decomposition methods. To test for neuroanatomical specificity, 16 specific tracts were additionally considered. We observed negative phenotypic correlations between epigenetic age acceleration and global white matter tract integrity (ρpheno=-0.119, p=0.028), with evidence of shared genetic (ρgene=-0.463, p=0.013) but not environmental influences. Negative phenotypic and genetic correlations with age acceleration were also seen for a number of specific white matter tracts, along with additional negative phenotypic correlations between granulocyte abundance and white matter integrity. These findings that increased acceleration in epigenetic age in peripheral blood correlates with reduced white matter integrity in the brain, and shares common genetic influences. provide a window into the neurobiology of aging processes within the brain and a potential biomarker of normal and pathological brain aging.SIGNIFICANCE STATEMENTEpigenetic measures can be used to predict age with a high degree of accuracy and so capture acceleration in biological age

  10. The Hippocampal Neuroproteome with Aging and Cognitive Decline: Past Progress and Future Directions

    PubMed Central

    VanGuilder, Heather D.; Freeman, Willard M.

    2011-01-01

    Although steady progress on understanding brain aging has been made over recent decades through standard anatomical, immunohistochemical, and biochemical techniques, the biological basis of non-neurodegenerative cognitive decline with aging remains to be determined. This is due in part to technical limitations of traditional approaches, in which only a small fraction of neurobiologically relevant proteins, mRNAs or metabolites can be assessed at a time. With the development and refinement of proteomic technologies that enable simultaneous quantitative assessment of hundreds to thousands of proteins, neuroproteomic studies of brain aging and cognitive decline are becoming more widespread. This review focuses on the contributions of neuroproteomic investigations to advances in our understanding of age-related deficits of hippocampus-dependent spatial learning and memory. Accumulating neuroproteomic data demonstrate that hippocampal aging involves common themes of dysregulated metabolism, increased oxidative stress, altered protein processing, and decreased synaptic function. Additionally, growing evidence suggests that cognitive decline does not represent a “more aged” phenotype, but rather is associated with specific neuroproteomic changes that occur in addition to age-related alterations. Understanding if and how age-related changes in the hippocampal neuroproteome contribute to cognitive decline and elucidating the pathways and processes that lead to cognitive decline are critical objectives that remain to be achieved. Progress in the field and challenges that remain to be addressed with regard to animal models, behavioral testing, and proteomic reporting are also discussed. PMID:21647399

  11. The many faces of human ageing: toward a psychological culture of old age.

    PubMed

    Baltes, P B

    1991-11-01

    In an effort to distil major findings about the nature of human ageing, seven propositions are presented as a guiding frame of reference. This propositional framework is then used to specify some conditions for a positive culture of old age and to advance one possible model of good psychological ageing. This model focuses on the dynamic interplay between three processes: selection, optimization, and compensation. The model is universal in its basic features, but at the same time emphasizes individual variations in phenotypic manifestation.

  12. Establishment of Human Papillomavirus Infection Requires Cell Cycle Progression

    PubMed Central

    Pyeon, Dohun; Pearce, Shane M.; Lank, Simon M.; Ahlquist, Paul; Lambert, Paul F.

    2009-01-01

    Human papillomaviruses (HPVs) are DNA viruses associated with major human cancers. As such there is a strong interest in developing new means, such as vaccines and microbicides, to prevent HPV infections. Developing the latter requires a better understanding of the infectious life cycle of HPVs. The HPV infectious life cycle is closely linked to the differentiation state of the stratified epithelium it infects, with progeny virus only made in the terminally differentiating suprabasal compartment. It has long been recognized that HPV must first establish its infection within the basal layer of stratified epithelium, but why this is the case has not been understood. In part this restriction might reflect specificity of expression of entry receptors. However, this hypothesis could not fully explain the differentiation restriction of HPV infection, since many cell types can be infected with HPVs in monolayer cell culture. Here, we used chemical biology approaches to reveal that cell cycle progression through mitosis is critical for HPV infection. Using infectious HPV16 particles containing the intact viral genome, G1-synchronized human keratinocytes as hosts, and early viral gene expression as a readout for infection, we learned that the recipient cell must enter M phase (mitosis) for HPV infection to take place. Late M phase inhibitors had no effect on infection, whereas G1, S, G2, and early M phase cell cycle inhibitors efficiently prevented infection. We conclude that host cells need to pass through early prophase for successful onset of transcription of the HPV encapsidated genes. These findings provide one reason why HPVs initially establish infections in the basal compartment of stratified epithelia. Only this compartment of the epithelium contains cells progressing through the cell cycle, and therefore it is only in these cells that HPVs can establish their infection. By defining a major condition for cell susceptibility to HPV infection, these results also have

  13. Glycosaminoglycans in the Human Cornea: Age-Related Changes

    PubMed Central

    Pacella, Elena; Pacella, Fernanda; De Paolis, Giulio; Parisella, Francesca Romana; Turchetti, Paolo; Anello, Giulia; Cavallotti, Carlo

    2015-01-01

    AIM To investigate possible age-related changes in glycosaminoglycans (GAGs) in the human cornea. The substances today called GAGs were previously referred to as mucopolysaccharides. METHODS Samples of human cornea were taken from 12 younger (age 21 ± 1.2) and 12 older (age 72 ± 1.6) male subjects. Samples were weighed, homogenized, and used for biochemical and molecular analyses. All the quantitative results were statistically analyzed. RESULTS The human cornea appears to undergo age-related changes, as evidenced by our biochemical and molecular results. The total GAG and hyaluronic acid counts were significantly higher in the younger subjects than in the older subjects. The sulfated heavy GAGs, such as chondroitin, dermatan, keratan, and heparan sulfate, were lower in the younger subjects than in the older subjects. DISCUSSION GAGs of the human cornea undergo numerous age-related changes. Their quantity is significantly altered in the elderly in comparison with younger subjects. GAGs play an important role in age-related diseases of the human cornea. PMID:25674020

  14. Age estimation based on aspartic acid racemization in human sclera.

    PubMed

    Klumb, Karolin; Matzenauer, Christian; Reckert, Alexandra; Lehmann, Klaus; Ritz-Timme, Stefanie

    2016-01-01

    Age estimation based on racemization of aspartic acid residues (AAR) in permanent proteins has been established in forensic medicine for years. While dentine is the tissue of choice for this molecular method of age estimation, teeth are not always available which leads to the need to identify other suitable tissues. We examined the suitability of total tissue samples of human sclera for the estimation of age at death. Sixty-five samples of scleral tissue were analyzed. The samples were hydrolyzed and after derivatization, the extent of aspartic acid racemization was determined by gas chromatography. The degree of AAR increased with age. In samples from younger individuals, the correlation of age and D-aspartic acid content was closer than in samples from older individuals. The age-dependent racemization in total tissue samples proves that permanent or at least long-living proteins are present in scleral tissue. The correlation of AAR in human sclera and age at death is close enough to serve as basis for age estimation. However, the precision of age estimation by this method is lower than that of age estimation based on the analysis of dentine which is due to molecular inhomogeneities of total tissue samples of sclera. Nevertheless, the approach may serve as a valuable alternative or addition in exceptional cases.

  15. Physical mapping of human chromosome 16. Annual progress report

    SciTech Connect

    Sutherland, G.R.

    1993-08-01

    We aim to isolate cDNAs mapping to human chromosome 16 and localise such cDNAs on the high resolution physical map. In collaboration with LANL, PCR primers will be synthesised from cDNA sequences mapped to chromosome 16 and used as ESTs in the generation of mega-YAC contigs for this chromosome. Probing of high density cosmid grids will enable integration of the ESTs into cosmid contigs and location of the cosmid contigs on the YAC contig. A hn-cDNA library has been constructed from the hybrid CY18 which contains chromosome 16 as the only human chromosome. A modified screening protocol has been successfully developed and 15 hn-cDNA clones have been sequenced and localised on the hybrid map. Sequence analysis of four of these revealed that they were known cDNAs, which are now mapped to chromosome 16. Development of techniques to allow the isolation of longer cDNAs from the identified exons is in progress. This will depend on PCR amplification of cDNAs from a total human CDNA library.

  16. [Progression of treatment and researches in dry age related macular degeneration].

    PubMed

    Zhang, Kaiyan; Tang, Shibo

    2015-03-01

    Age related macular degeneration (AMD) is the leading cause of blindness and visual disability among old patients in Europe and North America. AMD has been divided into two broad clinical categories depending on whether there is a presence of abnormal neovascularization: neovascular (exudative or wet) AMD and dry (or geographic atrophic) AMD. VEGF has been understood as a pathogenesis of wet AMD which allows us to get breakthroughs in treatment. While the progression of dry AMD treatment is very slow because the lack of pathogenesis, no acute loss of vision, and without appropriate standards for treatment. This review tries to introduce about the recent researches and progressions for dry AMD treatment.

  17. Stratigraphic placement and age of modern humans from Kibish, Ethiopia.

    PubMed

    McDougall, Ian; Brown, Francis H; Fleagle, John G

    2005-02-17

    In 1967 the Kibish Formation in southern Ethiopia yielded hominid cranial remains identified as early anatomically modern humans, assigned to Homo sapiens. However, the provenance and age of the fossils have been much debated. Here we confirm that the Omo I and Omo II hominid fossils are from similar stratigraphic levels in Member I of the Kibish Formation, despite the view that Omo I is more modern in appearance than Omo II. 40Ar/39Ar ages on feldspar crystals from pumice clasts within a tuff in Member I below the hominid levels place an older limit of 198 +/- 14 kyr (weighted mean age 196 +/- 2 kyr) on the hominids. A younger age limit of 104 +/- 7 kyr is provided by feldspars from pumice clasts in a Member III tuff. Geological evidence indicates rapid deposition of each member of the Kibish Formation. Isotopic ages on the Kibish Formation correspond to ages of Mediterranean sapropels, which reflect increased flow of the Nile River, and necessarily increased flow of the Omo River. Thus the 40Ar/39Ar age measurements, together with the sapropel correlations, indicate that the hominid fossils have an age close to the older limit. Our preferred estimate of the age of the Kibish hominids is 195 +/- 5 kyr, making them the earliest well-dated anatomically modern humans yet described.

  18. Evidence for the hallmarks of human aging in replicatively aging yeast

    PubMed Central

    Janssens, Georges E.; Veenhoff, Liesbeth M.

    2016-01-01

    Recently, efforts have been made to characterize the hallmarks that accompany and contribute to the phenomenon of aging, as most relevant for humans 1. Remarkably, studying the finite lifespan of the single cell eukaryote budding yeast (recently reviewed in 2 and 3) has been paramount for our understanding of aging. Here, we compile observations from literature over the past decades of research on replicatively aging yeast to highlight how the hallmarks of aging in humans are present in yeast. We find strong evidence for the majority of these, and summarize how yeast aging is especially characterized by the hallmarks of genomic instability, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, and mitochondrial dysfunction. PMID:28357364

  19. Human Pituitary Adenoma Proteomics: New Progresses and Perspectives

    PubMed Central

    Zhan, Xianquan; Wang, Xiaowei; Cheng, Tingting

    2016-01-01

    Pituitary adenoma (PA) is a common intracranial neoplasm that impacts on human health through interfering hypothalamus–pituitary–target organ axis systems. The development of proteomics gives great promises in the clarification of molecular mechanisms of a PA and discovery of effective biomarkers for prediction, prevention, early-stage diagnosis, and treatment for a PA. A great progress in the field of PA proteomics has been made in the past 10 years, including (i) the use of laser-capture microdissection, (ii) proteomics analyses of functional PAs (such as prolactinoma), invasive and non-invasive non-functional pituitary adenomas (NFPAs), protein post-translational modifications such as phosphorylation and tyrosine nitration, NFPA heterogeneity, and hormone isoforms, (iii) the use of protein antibody array, (iv) serum proteomics and peptidomics, (v) the integration of proteomics and other omics data, and (vi) the proposal of multi-parameter systematic strategy for a PA. This review will summarize these progresses of proteomics in PAs, point out the existing drawbacks, propose the future research directions, and address the clinical relevance of PA proteomics data, in order to achieve our long-term goal that is use of proteomics to clarify molecular mechanisms, construct molecular networks, and discover effective biomarkers. PMID:27303365

  20. Korean Contribution to the Progress of Science and Humanity

    NASA Astrophysics Data System (ADS)

    Min, Dong-Pil

    2012-03-01

    Science has problems yet to solve those global issues as the climate change, nuclear waste, water pollution, etc, although science and technology have been major contributors to human progress and will continue to open new doors to economic, medical and environmental advancement. Furthermore the benefits of scientific knowledge are not readily and evenly allocated across the globe. Korea will contribute to the progress of science by providing cooperative opportunities of the future research on the pure and applied scientific issues. Recently Korea launches a project of construction of the rare isotope accelerator, KoRIA, and Institute of Basic Science. Plans are set also to help develop the appropriate technology for developing countries. In this talk two aspects of science policy of Korean government are introduced, which are related to the accelerator KoRIA and to the thought on the establishment of Common Technology Platform. The former is to help the world science society for the expansion of our knowledge on the universe and matter, while the latter is to help the transfer of our knowledge to make our planet more flat.

  1. Influence of age, irradiation and humanization on NSG mouse phenotypes

    PubMed Central

    Knibbe-Hollinger, Jaclyn S.; Fields, Natasha R.; Chaudoin, Tammy R; Epstein, Adrian A.; Makarov, Edward; Akhter, Sidra P.; Gorantla, Santhi; Bonasera, Stephen J.; Gendelman, Howard E.; Poluektova, Larisa Y.

    2015-01-01

    ABSTRACT Humanized mice are frequently utilized in bench to bedside therapeutic tests to combat human infectious, cancerous and degenerative diseases. For the fields of hematology-oncology, regenerative medicine, and infectious diseases, the immune deficient mice have been used commonly in basic research efforts. Obstacles in true translational efforts abound, as the relationship between mouse and human cells in disease pathogenesis and therapeutic studies requires lengthy investigations. The interplay between human immunity and mouse biology proves ever more complicated when aging, irradiation, and human immune reconstitution are considered. All can affect a range of biochemical and behavioral functions. To such ends, we show age- and irradiation-dependent influences for the development of macrocytic hyper chromic anemia, myelodysplasia, blood protein reductions and body composition changes. Humanization contributes to hematologic abnormalities. Home cage behavior revealed day and dark cycle locomotion also influenced by human cell reconstitutions. Significant age-related day-to-day variability in movement, feeding and drinking behaviors were observed. We posit that this data serves to enable researchers to better design translational studies in this rapidly emerging field of mouse humanization. PMID:26353862

  2. Influence of age, irradiation and humanization on NSG mouse phenotypes.

    PubMed

    Knibbe-Hollinger, Jaclyn S; Fields, Natasha R; Chaudoin, Tammy R; Epstein, Adrian A; Makarov, Edward; Akhter, Sidra P; Gorantla, Santhi; Bonasera, Stephen J; Gendelman, Howard E; Poluektova, Larisa Y

    2015-09-09

    Humanized mice are frequently utilized in bench to bedside therapeutic tests to combat human infectious, cancerous and degenerative diseases. For the fields of hematology-oncology, regenerative medicine, and infectious diseases, the immune deficient mice have been used commonly in basic research efforts. Obstacles in true translational efforts abound, as the relationship between mouse and human cells in disease pathogenesis and therapeutic studies requires lengthy investigations. The interplay between human immunity and mouse biology proves ever more complicated when aging, irradiation, and human immune reconstitution are considered. All can affect a range of biochemical and behavioral functions. To such ends, we show age- and irradiation-dependent influences for the development of macrocytic hyper chromic anemia, myelodysplasia, blood protein reductions and body composition changes. Humanization contributes to hematologic abnormalities. Home cage behavior revealed day and dark cycle locomotion also influenced by human cell reconstitutions. Significant age-related day-to-day variability in movement, feeding and drinking behaviors were observed. We posit that this data serves to enable researchers to better design translational studies in this rapidly emerging field of mouse humanization.

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

    PubMed

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

    2008-05-01

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

  4. Increased mobilization of aged carbon to rivers by human disturbance

    NASA Astrophysics Data System (ADS)

    Butman, David E.; Wilson, Henry F.; Barnes, Rebecca T.; Xenopoulos, Marguerite A.; Raymond, Peter A.

    2015-02-01

    Approximately 8% of anthropogenic carbon dioxide emissions are estimated to come from land-use change, but this estimate excludes fluxes of terrestrial carbon to aquatic ecosystems from human disturbance. Carbon fluxes from land to rivers have probably increased by 0.1 to 0.2 petagrams of carbon per year as a result of disturbances such as deforestation, agricultural intensification and the injection of human wastewater. Most dissolved organic carbon in rivers originates from young organic carbon from soils and vegetation, but aged carbon removed from the modern carbon cycle is also exported in many systems. Here we analyse a global data set of radiocarbon ages of riverine dissolved organic carbon and spatial data on land cover, population and environmental variables. We find that the age of dissolved organic carbon in rivers increases with population density and the proportion of human-dominated landscapes within a watershed, and decreases with annual precipitation. We reason that disturbance reintroduces aged soil organic matter into the modern carbon cycle, although fossil carbon in fertilizer or petroleum products may also be a source of aged carbon in disturbed watersheds. The total export from the terrestrial environment to freshwater systems remains unknown; nevertheless, our results suggest that 3-9% of dissolved organic carbon in rivers is aged carbon mobilized by human disturbance.

  5. Yeast Cells Expressing the Human Mitochondrial DNA Polymerase Reveal Correlations between Polymerase Fidelity and Human Disease Progression*

    PubMed Central

    Qian, Yufeng; Kachroo, Aashiq H.; Yellman, Christopher M.; Marcotte, Edward M.; Johnson, Kenneth A.

    2014-01-01

    Mutations in the human mitochondrial polymerase (polymerase-γ (Pol-γ)) are associated with various mitochondrial disorders, including mitochondrial DNA (mtDNA) depletion syndrome, Alpers syndrome, and progressive external opthamalplegia. To correlate biochemically quantifiable defects resulting from point mutations in Pol-γ with their physiological consequences, we created “humanized” yeast, replacing the yeast mtDNA polymerase (MIP1) with human Pol-γ. Despite differences in the replication and repair mechanism, we show that the human polymerase efficiently complements the yeast mip1 knockouts, suggesting common fundamental mechanisms of replication and conserved interactions between the human polymerase and other components of the replisome. We also examined the effects of four disease-related point mutations (S305R, H932Y, Y951N, and Y955C) and an exonuclease-deficient mutant (D198A/E200A). In haploid cells, each mutant results in rapid mtDNA depletion, increased mutation frequency, and mitochondrial dysfunction. Mutation frequencies measured in vivo equal those measured with purified enzyme in vitro. In heterozygous diploid cells, wild-type Pol-γ suppresses mutation-associated growth defects, but continuous growth eventually leads to aerobic respiration defects, reduced mtDNA content, and depolarized mitochondrial membranes. The severity of the Pol-γ mutant phenotype in heterozygous diploid humanized yeast correlates with the approximate age of disease onset and the severity of symptoms observed in humans. PMID:24398692

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

    PubMed Central

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

    2012-01-01

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

  7. In silico regulatory analysis for exploring human disease progression

    PubMed Central

    Holloway, Dustin T; Kon, Mark; DeLisi, Charles

    2008-01-01

    Background An important goal in bioinformatics is to unravel the network of transcription factors (TFs) and their targets. This is important in the human genome, where many TFs are involved in disease progression. Here, classification methods are applied to identify new targets for 152 transcriptional regulators using publicly-available targets as training examples. Three types of sequence information are used: composition, conservation, and overrepresentation. Results Starting with 8817 TF-target interactions we predict an additional 9333 targets for 152 TFs. Randomized classifiers make few predictions (~2/18660) indicating that our predictions for many TFs are significantly enriched for true targets. An enrichment score is calculated and used to filter new predictions. Two case-studies for the TFs OCT4 and WT1 illustrate the usefulness of our predictions: • Many predicted OCT4 targets fall into the Wnt-pathway. This is consistent with known biology as OCT4 is developmentally related and Wnt pathway plays a role in early development. • Beginning with 15 known targets, 354 predictions are made for WT1. WT1 has a role in formation of Wilms' tumor. Chromosomal regions previously implicated in Wilms' tumor by cytological evidence are statistically enriched in predicted WT1 targets. These findings may shed light on Wilms' tumor progression, suggesting that the tumor progresses either by loss of WT1 or by loss of regions harbouring its targets. • Targets of WT1 are statistically enriched for cancer related functions including metastasis and apoptosis. Among new targets are BAX and PDE4B, which may help mediate the established anti-apoptotic effects of WT1. • Of the thirteen TFs found which co-regulate genes with WT1 (p ≤ 0.02), 8 have been previously implicated in cancer. The regulatory-network for WT1 targets in genomic regions relevant to Wilms' tumor is provided. Conclusion We have assembled a set of features for the targets of human TFs and used them to

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

    PubMed

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

    2015-03-01

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

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

    SciTech Connect

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

    2015-03-01

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

  10. Progressive Bidirectional Age-Related Changes in Default Mode Network Effective Connectivity across Six Decades.

    PubMed

    Li, Karl; Laird, Angela R; Price, Larry R; McKay, D Reese; Blangero, John; Glahn, David C; Fox, Peter T

    2016-01-01

    The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20-29 to 70-79). Structural equation modeling (SEM) was used to assess age-related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age-related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging.

  11. Progressive Bidirectional Age-Related Changes in Default Mode Network Effective Connectivity across Six Decades

    PubMed Central

    Li, Karl; Laird, Angela R.; Price, Larry R.; McKay, D. Reese; Blangero, John; Glahn, David C.; Fox, Peter T.

    2016-01-01

    The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20–29 to 70–79). Structural equation modeling (SEM) was used to assess age-related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age-related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging. PMID:27378909

  12. Human podocyte depletion in association with older age and hypertension.

    PubMed

    Puelles, Victor G; Cullen-McEwen, Luise A; Taylor, Georgina E; Li, Jinhua; Hughson, Michael D; Kerr, Peter G; Hoy, Wendy E; Bertram, John F

    2016-04-01

    Podocyte depletion plays a major role in the development and progression of glomerulosclerosis. Many kidney diseases are more common in older age and often coexist with hypertension. We hypothesized that podocyte depletion develops in association with older age and is exacerbated by hypertension. Kidneys from 19 adult Caucasian American males without overt renal disease were collected at autopsy in Mississippi. Demographic data were obtained from medical and autopsy records. Subjects were categorized by age and hypertension as potential independent and additive contributors to podocyte depletion. Design-based stereology was used to estimate individual glomerular volume and total podocyte number per glomerulus, which allowed the calculation of podocyte density (number per volume). Podocyte depletion was defined as a reduction in podocyte number (absolute depletion) or podocyte density (relative depletion). The cortical location of glomeruli (outer or inner cortex) and presence of parietal podocytes were also recorded. Older age was an independent contributor to both absolute and relative podocyte depletion, featuring glomerular hypertrophy, podocyte loss, and thus reduced podocyte density. Hypertension was an independent contributor to relative podocyte depletion by exacerbating glomerular hypertrophy, mostly in glomeruli from the inner cortex. However, hypertension was not associated with podocyte loss. Absolute and relative podocyte depletion were exacerbated by the combination of older age and hypertension. The proportion of glomeruli with parietal podocytes increased with age but not with hypertension alone. These findings demonstrate that older age and hypertension are independent and additive contributors to podocyte depletion in white American men without kidney disease.

  13. Utility of the frontonasal suture for estimating age at death in human skeletal remains.

    PubMed

    Alesbury, Helen S; Ubelaker, Douglas H; Bernstein, Robin

    2013-01-01

    This project evaluated the utility of the frontonasal suture for estimating age at death. Utilizing human remains of known age at death with varying degrees of fusion, curated at the American Museum of Natural History in New York City and the Smithsonian Institution's National Museum of Natural History in Washington, DC, data were collected from the ectocranial surface of 522 crania; 68 of these were sagittally sectioned, allowing collection of internal data and observation of suture closure through the bone. Degree of ectocranial suture closure does not significantly predict age, even when sex and ancestry are accounted for. Suture closure progression data were converted into a Hershkovitz ratio (sum of the measurement of open portion divided by the total suture length), and regression models demonstrate that the effect of age accounts for only 13% of variation in suture closure.

  14. Do glutathione levels decline in aging human brain?

    PubMed

    Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

    2016-04-01

    For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain.

  15. Expression of NM23 in human melanoma progression and metastasis.

    PubMed Central

    Easty, D. J.; Maung, K.; Lascu, I.; Véron, M.; Fallowfield, M. E.; Hart, I. R.; Bennett, D. C.

    1996-01-01

    NM23 is a putative metastasis-suppressor gene for some human cancers. Here we have studied NM23 expression during melanoma progression using Northern blotting and immunocytochemistry. There was no significant difference in the average amounts of NM23 mRNA between cell lines derived from metastatic and primary melanomas. The level of NM23 mRNA was also determined for three pairs of poorly metastatic parental (P) and their highly metastatic variant (M) cell lines; the ratios for M/P were 1.2, 0.98 and 0.80. Next we used immunocytochemistry to study NM23 protein in normal skin, benign naevi and primary and metastatic melanomas. Melanocytes in all normal skin and benign samples were positive for NM23; however most primary melanomas (7/11) were not stained by the antibody. All metastatic melanoma samples (5/5) were positively stained. Findings were similar with an antiserum reactive with both forms of NM23 (H1 and H2), and with an antibody specific for NM23-H1. No relationship was apparent between NM23 immunoreactivity in primary tumours and their aggressiveness or prognosis. Hence, in contrast to the situation described for murine melanoma, the amount of NM23 mRNA or protein in human melanoma did not correlate inversely with metastasis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8679442

  16. Detection of advanced glycation end products (AGEs) on human skin by in vivo confocal Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Martin, A. A.; Pereira, L.; Ali, S. M.; Pizzol, C. D.; Tellez, C. A.; Favero, P. P.; Santos, L.; da Silva, V. V.; Praes, C. E. O.

    2016-03-01

    The aging process involves the reduction in the production of the major components of skin tissue. During intrinsic aging and photoaging processes, in dermis of human skin, fibroblasts become senescent and have decreased activity, which produce low levels of collagen. Moreover, there is accumulation of advanced glycation end products (AGEs). AGEs have incidence in the progression of age-related diseases, principally in diabetes mellitus and in Alzheimer's diseases. AGEs causes intracellular damage and/or apoptosis leading to an increase of the free radicals, generating a crosslink with skin proteins and oxidative stress. The aim of this study is to detect AGEs markers on human skin by in vivo Confocal Raman spectroscopy. Spectra were obtained by using a Rivers Diagnostic System, 785 nm laser excitation and a CCD detector from the skin surface down to 120 μm depth. We analyzed the confocal Raman spectra of the skin dermis of 30 women volunteers divided into 3 groups: 10 volunteers with diabetes mellitus type II, 65-80 years old (DEW); 10 young healthy women, 20-33 years old (HYW); and 10 elderly healthy women, 65-80 years old (HEW). Pentosidine and glucosepane were the principally identified AGEs in the hydroxyproline and proline Raman spectral region (1000-800 cm-1), in the 1.260-1.320 cm-1 region assignable to alpha-helical amide III modes, and in the Amide I region. Pentosidine and glucosepane calculated vibrational spectra were performed through Density Functional Theory using the B3LYP functional with 3-21G basis set. Difference between the Raman spectra of diabetic elderly women and healthy young women, and between healthy elderly women and healthy young women were also obtained with the purpose of identifying AGEs Raman bands markers. AGEs peaks and collagen changes have been identified and used to quantify the glycation process in human skin.

  17. Aging

    PubMed Central

    Park, Dong Choon

    2013-01-01

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

  18. Decreases in Human Semen Quality with Age Among Healthy Men

    SciTech Connect

    Eskenazi, B.; Wyrobek, A.J.; Kidd, S.A.; Moore, L.; Young, S.S.; Moore, D.

    2001-12-01

    The objective of this report is to characterize the associations between age and semen quality among healthy active men after controlling for identified covariates. Ninety-seven healthy, nonsmoking men between 22 and 80 years without known fertility problems who worked for or retired from a large research laboratory. There was a gradual decrease in all semen parameters from 22-80 years of age. After adjusting for covariates, volume decreased 0.03 ml per year (p = 0.001); sperm concentration decreased 2.5% per year (p = 0.005); total count decreased 3.6% per year of age (p < 0.001); motility decreased 0.7% per year (P < 0.001); progressive motility decreased 3.1% per year (p < 0.001); and total progressively motile sperm decreased 4.8% per year (p < 0.001). In a group of healthy active men, semen volume, sperm concentration, total sperm count, and sperm motility decrease continuously between 22-80 years of age, with no evidence of a threshold.

  19. Variants in GBA, SNCA, and MAPT influence Parkinson disease risk, age at onset, and progression.

    PubMed

    Davis, Albert A; Andruska, Kristin M; Benitez, Bruno A; Racette, Brad A; Perlmutter, Joel S; Cruchaga, Carlos

    2016-01-01

    Multiple genetic variants have been linked to risk of Parkinson disease (PD), but known mutations do not explain a large proportion of the total PD cases. Similarly, multiple loci have been associated with PD risk by genome-wide association studies (GWAS). The influence that genetic factors confer on phenotypic diversity remains unclear. Few studies have been performed to determine whether the GWAS loci are also associated with age at onset (AAO) or motor progression. We used 2 PD case-control data sets (Washington University and the Parkinson's Progression Markers Initiative) to determine whether polymorphisms located at the GWAS top hits (GBA, ACMSD/TMEM163, STK39, MCCC1/LAMP3, GAK/TMEM175, SNCA, and MAPT) show association with AAO or motor progression. We found associations between single nucleotide polymorphisms at the GBA and MAPT loci and PD AAO and progression. These findings reinforce the complex genetic basis of PD and suggest that distinct genes and variants explain the genetic architecture of PD risk, onset, and progression.

  20. Cell Cycle Progression of Human Cells Cultured in Rotating Bioreactor

    NASA Technical Reports Server (NTRS)

    Parks, Kelsey

    2009-01-01

    Space flight has been shown to alter the astronauts immune systems. Because immune performance is complex and reflects the influence of multiple organ systems within the host, scientists sought to understand the potential impact of microgravity alone on the cellular mechanisms critical to immunity. Lymphocytes and their differentiated immature form, lymphoblasts, play an important and integral role in the body's defense system. T cells, one of the three major types of lymphocytes, play a central role in cell-mediated immunity. They can be distinguished from other lymphocyte types, such as B cells and natural killer cells by the presence of a special receptor on their cell surface called T cell receptors. Reported studies have shown that spaceflight can affect the expression of cell surface markers. Cell surface markers play an important role in the ability of cells to interact and to pass signals between different cells of the same phenotype and cells of different phenotypes. Recent evidence suggests that cell-cycle regulators are essential for T-cell function. To trigger an effective immune response, lymphocytes must proliferate. The objective of this project is to investigate the changes in growth of human cells cultured in rotating bioreactors and to measure the growth rate and the cell cycle distribution for different human cell types. Human lymphocytes and lymphoblasts will be cultured in a bioreactor to simulate aspects of microgravity. The bioreactor is a cylindrical culture vessel that incorporates the aspects of clinostatic rotation of a solid fluid body around a horizontal axis at a constant speed, and compensates gravity by rotation and places cells within the fluid body into a sustained free-fall. Cell cycle progression and cell proliferation of the lymphocytes will be measured for a number of days. In addition, RNA from the cells will be isolated for expression of genes related in cell cycle regulations.

  1. Lipofuscin Granules in the Epileptic Human Temporal Neocortex with Age.

    PubMed

    Merlo, Suélen; Nakayama, Ana Beatriz S; Brusco, Janaina; Rossi, Marcos A; Carlotti, Carlos G; Moreira, Jorge E

    2015-01-01

    Lipofuscin granules (LGs), the "age pigments", are autofluorescent cell products from lysosomes that diverge in number and size among brain regions. Human temporal cortex from 20- to 55-year-old epileptic subjects were studied with the fat soluble dye Sudan Black, under confocal and electron microscopy. Ultrastructural analysis showed that with age LGs increase in area, but not in number. Proportionally to the LGs area, the electron lucid portion increases and the electron dense reduces over time. The robust increase in lipid components is possibly due to modifications in the neuronal metabolism with age in physiological and pathological conditions.

  2. Human Aging Is a Metabolome-related Matter of Gender.

    PubMed

    Jové, Mariona; Maté, Ianire; Naudí, Alba; Mota-Martorell, Natalia; Portero-Otín, Manuel; De la Fuente, Mónica; Pamplona, Reinald

    2016-05-01

    A molecular description of the mechanisms by which aging is produced is still very limited. Here, we have determined the plasma metabolite profile by using high-throughput metabolome profiling technologies of 150 healthy humans ranging from 30 to 100 years of age. Using a nontargeted approach, we detected 2,678 metabolite species in plasma, and the multivariate analyses separated perfectly two groups indicating a specific signature for each gender. In addition, there is a set of gender-shared metabolites, which change significantly during aging with a similar tendency. Among the identified molecules, we found vitamin D2-related compound, phosphoserine (40:5), monoacylglyceride (22:1), diacylglyceride (33:2), and resolvin D6, all of them decreasing with the aging process. Finally, we found three molecules that directly correlate with age and seven that inversely correlate with age, independently of gender. Among the identified molecules (6 of 10 according to exact mass and retention time), we found a proteolytic product (l-γ-glutamyl-l-leucine), which increased with age. On the contrary, a hydroxyl fatty acid (25-hydroxy-hexacosanoic), a polyunsaturated fatty acid (eicosapentaenoic acid), two phospholipids (phosphocholine [42:9]and phosphoserine [42:3]) and a prostaglandin (15-keto-prostaglandin F2α) decreased with aging. These results suggest that lipid species and their metabolism are closely linked to the aging process.

  3. Aging in mouse and human systems: a comparative study.

    PubMed

    Demetrius, Lloyd

    2006-05-01

    This article discusses the significance of mouse models as a basis for elucidating the aging process in humans. We identify certain parallels between mouse and human systems and review the theoretical and empirical support for the claim that the large divergence in the rate of aging between the two species resides in differences in the stability of their metabolic networks. We will show that these differences in metabolic stability have their origin in the different ecological constraints the species experience during their evolutionary history. We exploit these ideas to compare the effect of caloric restriction on murine and human systems. The studies predict that the large increases in mean life span and maximum life-span potential observed in laboratory rodents subject to caloric restriction will not obtain in human populations. We predict that, in view of the different metabolic stability of the two systems, caloric restriction will have no effect on the maximum life-span potential of humans, and a relatively minor effect on the mean life span of nonobese populations. This article thus points to certain intrinsic limitations in the use of mouse models in elucidating the aging process in humans. We furthermore contend the view that these limitations can be mitigated by considering the metabolic stability of the two species.

  4. Molecular genetics of human cancer predisposition and progression.

    PubMed

    Cavenee, W K; Scrable, H J; James, C D

    1991-04-01

    The development of human cancer is generally thought to entail a series of events that cause a progressively more malignant phenotype. Such a hypothesis predicts that tumor cells of the ultimate stage will carry each of the events, cells of the penultimate stage will carry each of the events less the last one and so on. A dissection of the pathway from a normal cell to a fully malignant tumor may thus be viewed as the unraveling of a nested set of aberrations. In experiments designed to elucidate these events we have compared genotypic combinations at genomic loci defined by restriction endonuclease recognition site variation in normal and tumor tissues from patients with various forms and stages of cancer. The first step, inherited predisposition, is best described for retinoblastoma in which a recessive mutation of a locus residing in the 13q14 region of the genome is unmasked by aberrant, but specific, mitotic chromosomal segregation. Similar mechanisms involving the distal short arm of chromosome 17 are apparent in astrocytic tumors and the events are shared by cells in each malignancy state. DNA sequencing indicates that these events accomplish the homozygosis of mutant alleles of the p53 gene. Copy number amplification of the epidermal growth factor receptor gene occurs in intermediate and late-stage tumors whereas loss of heterozygosity for loci on chromosome 10 is restricted to the ultimate stage, glioblastoma multiforme. These results suggest a genetic approach to defining degrees of tumor progression and the locations of genes involved in the pathway as a prelude to their molecular isolation and characterization.

  5. The Human Right to Leisure in Old Age: Reinforcement of the Rights of an Aging Population.

    PubMed

    Karev, Iris; Doron, Israel Issi

    2016-11-23

    The right to leisure is recognized as a human right under the 1948 United Nations Universal Declaration of Human Rights. The actual meaning and material content of this human right is subject to debate. The aim of this study is to examine the extent and the context to which this human right is specifically recognized with regard to older persons. Methodologically, this study textually analyzed 17 different international older persons' human rights documents. The findings reveal that in the majority of these documents there is no reference to the right to leisure. In the remaining documents, the right to leisure is mostly referred to indirectly or in a narrow legal construction. These findings support the notion that despite the growing body of knowledge regarding the importance of meaningful leisure in old age-and its empowering and anti-ageist nature-this knowledge has not transformed into a legal human rights discourse.

  6. Stress-Activated Cap’n’collar Transcription Factors in Aging and Human Disease

    PubMed Central

    Sykiotis, Gerasimos P.; Bohmann, Dirk

    2010-01-01

    Cap’n’collar (Cnc) transcription factors are conserved in metazoans and have important developmental and homeostatic functions. The vertebrate Nrf1, Nrf2, and Nrf3, the Caenorhabditis elegans SKN-1, and the Drosophila CncC comprise a subgroup of Cnc factors that mediate adaptive responses to cellular stress. The most studied stress-activated Cnc factor is Nrf2, which orchestrates the transcriptional response of cells to oxidative stressors and electrophilic xenobiotics. In rodent models, signaling by Nrf2 defends against oxidative stress and aging-associated disorders, such as neurodegeneration, respiratory diseases, and cancer. In humans, polymorphisms that decrease Nrf2 abundance have been associated with various pathologies of the skin, respiratory system, and digestive tract. In addition to preventing disease in rodents and humans, Cnc factors have lifespan-extending and anti-aging functions in invertebrates. However, despite the pro-longevity and antioxidant roles of stress-activated Cnc factors, their activity paradoxically declines in aging model organisms and in humans suffering from progressing respiratory disease or neurodegeneration. We review the roles and regulation of stress-activated Cnc factors across species, present all reported instances in which their activity is paradoxically decreased in aging and disease, and discuss the possibility that the pharmacological restoration of Nrf2 signaling may be useful in the prevention and treatment of age-related diseases. PMID:20215646

  7. Magnesium and fluoride distribution in human cementum with age.

    PubMed

    Tsuboi, S; Nakagaki, H; Takami, Y; Eba, H; Kirkham, J; Robinson, C

    2000-12-01

    Sixty-two human teeth, obtained from subjects aged 11 to 80 years, were used to determine the magnesium and fluoride concentration and distribution with age in human cementum. Transverse sections were prepared from the root region of teeth. Samples, each 30 microm thick, were abraded in sequence from the cementum surface and the cemento-dentine junction by an abrasive micro-sampling technique. Magnesium concentrations were lower in the cementum surface, and increased towards the cemento-dentine junction (CDJ), while fluoride concentrations were higher in cementum surfaces and tended to decrease towards CDJ. Fluoride distribution patterns were similar to that reported earlier while average fluoride concentration increased with age, however, either no change or decreasing tendencies were observed with magnesium.

  8. Age effects in the human middle ear: Wideband acoustical measures

    NASA Astrophysics Data System (ADS)

    Feeney, M. Patrick; Sanford, Chris A.

    2004-12-01

    Studies that have examined age effects in the human middle ear using either admittance measures at 220 or 660 Hz or multifrequency tympanometry from 200 to 2000 Hz have had conflicting results. Several studies have suggested an increase in admittance with age, while several others have suggested a decrease in admittance with age. A third group of studies found no significant age effect. This study examined 226 Hz tympanometry and wideband energy reflectance and impedance at ambient pressure in a group of 40 young adults and a group of 30 adults with age >=60 years. The groups did not differ in admittance measures of the middle ear at 226 Hz. However, significant age effects were found in wideband energy reflectance and impedance. In particular, in older adults there was a comparative decrease in reflectance from 800 to 2000 Hz but an increase near 4000 Hz. The results suggest a decrease in middle-ear stiffness with age. The findings of this study hold relevance for understanding the aging process in the auditory system, for the establishment of normative data for wideband energy reflectance, for the possibility of a conductive component to presbycusis, and for the interpretation of otoacoustic emission measurements. .

  9. Progression of Cardio-Metabolic Risk Factors in Subjects Born Small and Large for Gestational Age

    PubMed Central

    Chiavaroli, Valentina; Marcovecchio, Maria Loredana; de Giorgis, Tommaso; Diesse, Laura; Chiarelli, Francesco; Mohn, Angelika

    2014-01-01

    Background Subjects born small (SGA) and large (LGA) for gestational age have an increased risk of cardio-metabolic alterations already during prepuberty. Nevertheless, the progression of their cardio-metabolic profile from childhood to adolescence has not been fully explored. Our aim was to assess potential changes in the cardio-metabolic profile from childhood to adolescence in subjects born SGA and LGA compared to those born appropriate (AGA) for gestational age. Methods This longitudinal study included 35 AGA, 24 SGA and 31 LGA subjects evaluated during childhood (mean age (±SD) 8.4±1.4 yr) and then re-assessed during adolescence (mean age 13.3±1.8 yr). BMI, blood pressure, insulin resistance (fasting insulin, HOMA-IR) and lipids were assessed. A cardio-metabolic risk z-score was applied and this consisted in calculating the sum of sex-specific z-scores for BMI, blood pressure, HOMA-IR, triglycerides and triglycerides:high-density lipoprotein cholesterol ratio. Results Fasting insulin and HOMA-IR were higher in SGA and LGA than AGA subjects both during childhood (all P<0.01) and adolescence (all P<0.01). Similarly, the clustered cardio-metabolic risk score was higher in SGA and LGA than AGA children (both P<0.05), and these differences among groups increased during adolescence (both P<0.05). Of note, a progression of the clustered cardio-metabolic risk score was observed from childhood to adolescence within SGA and within LGA subjects (both P<0.05). Conclusions SGA and LGA subjects showed an adverse cardio-metabolic profile during childhood when compared to AGA peers, with a worsening of this profile during adolescence. These findings indicate an overtime progression of insulin resistance and overall estimated cardiovascular risk from childhood to adolescence in SGA and LGA populations. PMID:25117750

  10. The Laboratory Rat: Relating Its Age With Human's

    PubMed Central

    Sengupta, Pallav

    2013-01-01

    By late 18th or early 19th century, albino rats became the most commonly used experimental animals in numerous biomedical researches, as they have been recognized as the preeminent model mammalian system. But, the precise correlation between age of laboratory rats and human is still a subject of debate. A number of studies have tried to detect these correlations in various ways, But, have not successfully provided any proper association. Thus, the current review attempts to compare rat and human age at different phases of their life. The overall findings indicate that rats grow rapidly during their childhood and become sexually mature at about the sixth week, but attain social maturity 5-6 months later. In adulthood, every day of the animal is approximately equivalent to 34.8 human days (i.e., one rat month is comparable to three human years). Numerous researchers performed experimental investigations in albino rats and estimated, in general, while considering their entire life span, that a human month resembles every-day life of a laboratory rat. These differences signify the variations in their anatomy, physiology and developmental processes, which must be taken into consideration while analyzing the results or selecting the dose of any research in rats when age is a crucial factor. PMID:23930179

  11. Rates and risk factors for progression to incident dementia vary by age in a population cohort

    PubMed Central

    Lee, Ching-Wen; Snitz, Beth E.; Hughes, Tiffany F.; McDade, Eric; Chang, Chung-Chou H.

    2015-01-01

    Objective: To estimate rate of progression from normal cognition or mild impairment to dementia, and to identify potential risk and protective factors for incident dementia, based on age at dementia onset in a prospective study of a population-based cohort (n = 1,982) aged 65 years and older. Methods: Following the cohort annually for up to 5 years, we estimated incidence of dementia (Clinical Dementia Rating ≥1) among individuals previously normal or mildly impaired (Clinical Dementia Rating 0 or 0.5). In the whole cohort, and also stratified by median onset age, we examined several vascular, metabolic, and inflammatory variables as potential risk factors for developing dementia, using interval-censored survival models. Results: Based on 67 incident cases of dementia, incidence rate (per 1,000 person-years) was 10.0 overall, 5.8 in those with median onset age of 87 years or younger, and 31.5 in those with onset age after 87 years. Adjusting for demographics, the risk of incident dementia with onset age of 87 years or younger (n = 33) was significantly increased by baseline smoking, stroke, low systolic blood pressure, and APOE*4 genotype, and reduced by current alcohol use. Among those with dementia with onset after 87 years (n = 34), no risk or protective factor was significant. Conclusion: Risk and protective factors were only found for incident dementia with onset before the median onset age of 87 years, and not for those with later onset. Either unexplored risk factors explain the continued increase in incidence with age, or unknown protective factors are allowing some individuals to delay onset into very old age. PMID:25471390

  12. Interventions to Slow Aging in Humans: Are We Ready?

    PubMed Central

    Longo, Valter D; Antebi, Adam; Bartke, Andrzej; Barzilai, Nir; Brown-Borg, Holly M; Caruso, Calogero; Curiel, Tyler J; de Cabo, Rafael; Franceschi, Claudio; Gems, David; Ingram, Donald K; Johnson, Thomas E; Kennedy, Brian K; Kenyon, Cynthia; Klein, Samuel; Kopchick, John J; Lepperdinger, Guenter; Madeo, Frank; Mirisola, Mario G; Mitchell, James R; Passarino, Giuseppe; Rudolph, Karl L; Sedivy, John M; Shadel, Gerald S; Sinclair, David A; Spindler, Stephen R; Suh, Yousin; Vijg, Jan; Vinciguerra, Manlio; Fontana, Luigi

    2015-01-01

    The workshop entitled ‘Interventions to Slow Aging in Humans: Are We Ready?’ was held in Erice, Italy, on October 8–13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consensus about all interventions, the participants selected a subset of the most promising strategies that could be tested in humans for their effects on healthspan. These were: (i) dietary interventions mimicking chronic dietary restriction (periodic fasting mimicking diets, protein restriction, etc.); (ii) drugs that inhibit the growth hormone/IGF-I axis; (iii) drugs that inhibit the mTOR–S6K pathway; or (iv) drugs that activate AMPK or specific sirtuins. These choices were based in part on consistent evidence for the pro-longevity effects and ability of these interventions to prevent or delay multiple age-related diseases and improve healthspan in simple model organisms and rodents and their potential to be safe and effective in extending human healthspan. The authors of this manuscript were speakers and discussants invited to the workshop. The following summary highlights the major points addressed and the conclusions of the meeting. PMID:25902704

  13. Interventions to Slow Aging in Humans: Are We Ready?

    PubMed

    Longo, Valter D; Antebi, Adam; Bartke, Andrzej; Barzilai, Nir; Brown-Borg, Holly M; Caruso, Calogero; Curiel, Tyler J; de Cabo, Rafael; Franceschi, Claudio; Gems, David; Ingram, Donald K; Johnson, Thomas E; Kennedy, Brian K; Kenyon, Cynthia; Klein, Samuel; Kopchick, John J; Lepperdinger, Guenter; Madeo, Frank; Mirisola, Mario G; Mitchell, James R; Passarino, Giuseppe; Rudolph, Karl L; Sedivy, John M; Shadel, Gerald S; Sinclair, David A; Spindler, Stephen R; Suh, Yousin; Vijg, Jan; Vinciguerra, Manlio; Fontana, Luigi

    2015-08-01

    The workshop entitled 'Interventions to Slow Aging in Humans: Are We Ready?' was held in Erice, Italy, on October 8-13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consensus about all interventions, the participants selected a subset of the most promising strategies that could be tested in humans for their effects on healthspan. These were: (i) dietary interventions mimicking chronic dietary restriction (periodic fasting mimicking diets, protein restriction, etc.); (ii) drugs that inhibit the growth hormone/IGF-I axis; (iii) drugs that inhibit the mTOR-S6K pathway; or (iv) drugs that activate AMPK or specific sirtuins. These choices were based in part on consistent evidence for the pro-longevity effects and ability of these interventions to prevent or delay multiple age-related diseases and improve healthspan in simple model organisms and rodents and their potential to be safe and effective in extending human healthspan. The authors of this manuscript were speakers and discussants invited to the workshop. The following summary highlights the major points addressed and the conclusions of the meeting.

  14. Effect of pre-freezing conditions on the progressive motility recovery rate of human frozen spermatozoa.

    PubMed

    Zhang, X; Zhou, Y; Xia, W; Wu, H; Yao, K; Liu, H; Xiong, C

    2012-10-01

    We evaluated the effects of sperm concentration, progressive motility, sperm morphology, duration of abstinence and collection season on the progressive motility recovery rate of human frozen spermatozoa to identify characteristics that predict the progressive motility recovery rate of human frozen spermatozoa and improve the protocol for sperm collecting in sperm banks. A total of 14 190 semen samples donated at Zhejiang human sperm bank of China between September 2006 and June 2011 were collected from 1624 donors. Semen was evaluated according to WHO standard procedures for sperm concentration. Progressive motility, sperm morphology, ejaculate collection season and abstinence time were recorded. After freezing and thawing, the progressive motility was assessed. Results showed that sperm concentration, progressive motility and normal morphology were significantly associated with the progressive motility recovery rate of human frozen spermatozoa. In addition, the abstinence time and collection season also significantly affected progressive motility recovery rate. Our results indicated that sperm concentration, progressive motility and normal morphology could be valuable in predicting the progressive motility recovery rate of human frozen spermatozoa. As such, progressive motility recovery may be improved by donating semen when abstinent for 3-5 days and during seasons other than summer.

  15. Effect of Progressive Muscle Relaxation on the Fatigue and Quality of Life Among Iranian Aging Persons.

    PubMed

    Hassanpour-Dehkordi, Ali; Jalali, Amir

    2016-07-01

    Since the elderly population is increasing rapidly in developing countries which may decrease the physical activity and exercise and in turn could affect the elderly's quality of life, this study aimed to investigate the effect of progressive muscle relaxation on the elderly's quality of life in Iran. In a randomized clinical trial, participants were randomly divided into intervention and control groups. For the intervention group, muscular progressive relaxation was run three days per week for three months (totally 36 sessions). In relaxation, a patient contract a group of his/her muscles in each step and relaxes them after five seconds and finally loosens all muscles and takes five deep breaths. Each session lasts for 45 minutes. The instrument of data gathering consisted of questionnaires on individual's demographic data and quality of life SF-36. After intervention, quality of life increased significantly in the patients undergoing muscular progressive relaxation and fatigue severity decreased significantly in the intervention group compared to prior to intervention. In addition, there was a statistically significant difference in mean score of physical performance, restricted activity after physical problem, energy, socially function, physical pain, overall hygiene, and quality of life between intervention and control groups. By implementing regular and continuous progressive muscle relaxation, quality of life could be increased in different dimensions in the elderly and the context could be provided to age healthily and enjoy higher health and autonomy. Therefore, all of the therapeutic staffs are recommended to implement this plan to promote the elderly's quality of life.

  16. Age-dependent and age-independent human memory persistence is enhanced by delayed posttraining methylphenidate administration

    PubMed Central

    Izquierdo, Iván; Bevilaqua, Lia R.; Rossato, Janine I.; Lima, Ramón H.; Medina, Jorge H.; Cammarota, Martín

    2008-01-01

    Healthy human volunteers 16–82 years of age with at least 10 years of schooling were exposed to two different memory tasks. The first task involved incidental memory. The subjects were asked, as casually as possible: “Did you watch any movie on TV 2 days ago? And 7 days ago? If so, do you remember the title of the movie(s) and the name of the first two actors (actresses)?” Retention scores (maximum = 3: title, actor 1, and actor 2) were equally high (overall mean = 2.6, n = 61) in all age groups (16–20, 21–30, 31–40, 41–60, and 61–82 years) for the day 2 scores. Scores for the movie seen 7 days before decreased significantly and progressively in the three older groups in relation to age, which indicates reduced persistence of this type of memory beginning at the age of 41–50 years and becoming more extensive over the years. The other task was a formal memory procedure. Subjects were asked to study a brief text with factual information on the 1954 World Soccer Cup for 10 min. They were then exposed to 10 questions on the text 2 days and, again, 7 days later. Retention scores declined between the two tests, but in this task, the decline of persistence occurred to a similar extent in all age groups, and thus was not dependent on age. Methylphenidate (10 mg p.o.) given 12 hours after acquisition markedly enhanced persistence of the two memory types. This suggests an involvement of dopaminergic processes in persistence in the late posttraining period. PMID:19050076

  17. Age-dependent and age-independent human memory persistence is enhanced by delayed posttraining methylphenidate administration.

    PubMed

    Izquierdo, Iván; Bevilaqua, Lia R; Rossato, Janine I; Lima, Ramón H; Medina, Jorge H; Cammarota, Martín

    2008-12-09

    Healthy human volunteers 16-82 years of age with at least 10 years of schooling were exposed to two different memory tasks. The first task involved incidental memory. The subjects were asked, as casually as possible: "Did you watch any movie on TV 2 days ago? And 7 days ago? If so, do you remember the title of the movie(s) and the name of the first two actors (actresses)?" Retention scores (maximum = 3: title, actor 1, and actor 2) were equally high (overall mean = 2.6, n = 61) in all age groups (16-20, 21-30, 31-40, 41-60, and 61-82 years) for the day 2 scores. Scores for the movie seen 7 days before decreased significantly and progressively in the three older groups in relation to age, which indicates reduced persistence of this type of memory beginning at the age of 41-50 years and becoming more extensive over the years. The other task was a formal memory procedure. Subjects were asked to study a brief text with factual information on the 1954 World Soccer Cup for 10 min. They were then exposed to 10 questions on the text 2 days and, again, 7 days later. Retention scores declined between the two tests, but in this task, the decline of persistence occurred to a similar extent in all age groups, and thus was not dependent on age. Methylphenidate (10 mg p.o.) given 12 hours after acquisition markedly enhanced persistence of the two memory types. This suggests an involvement of dopaminergic processes in persistence in the late posttraining period.

  18. Ultrastructural changes in the melanocytes of aging human choroid.

    PubMed

    Nag, Tapas Chandra

    2015-12-01

    Retinal pigment epithelial cells as well as choroidal melanocytes (CM) possess melanin granules. The former show clear, age-related changes (formation of lipofuscin granules with a concomitant decrease in melanin content); however, data on changes in the CM with aging are fairly limited. We examined CM in human macular and mid-peripheral areas by light- and transmission electron microscopy in 50-94 year-old donor eyes (N=12). Unlike in the choroid of lower ages, the melanocytes from aging choroid (>75 years) showed partial fusion of about 8-15 melanosomes, forming rosettes-like structures. Besides, there was evidence of emptiness in cytoplasm caused by the loss of melanosomes in aged CM, as was confirmed by quantification in macular part of choroid. In advanced aged eyes (85-94-year-old), the CM possessed many lipid droplets as well as irregular lipofuscin granules, the latter had a tendency to fuse with melanosomes, as happens in aged retinal pigment epithelium. Macrophages in their cytoplasm contained abundant irregular as well as clumped melanosomes of variable size, suggesting that damaged granules/melanocytes are cleared by these phagocytes. These obvious changes in the CM are likely to make the choroid prone to damage by visible light.

  19. EPHA2 is associated with age-related cortical cataract in mice and humans.

    PubMed

    Jun, Gyungah; Guo, Hong; Klein, Barbara E K; Klein, Ronald; Wang, Jie Jin; Mitchell, Paul; Miao, Hui; Lee, Kristine E; Joshi, Tripti; Buck, Matthias; Chugha, Preeti; Bardenstein, David; Klein, Alison P; Bailey-Wilson, Joan E; Gong, Xiaohua; Spector, Tim D; Andrew, Toby; Hammond, Christopher J; Elston, Robert C; Iyengar, Sudha K; Wang, Bingcheng

    2009-07-01

    Age-related cataract is a major cause of blindness worldwide, and cortical cataract is the second most prevalent type of age-related cataract. Although a significant fraction of age-related cataract is heritable, the genetic basis remains to be elucidated. We report that homozygous deletion of Epha2 in two independent strains of mice developed progressive cortical cataract. Retroillumination revealed development of cortical vacuoles at one month of age; visible cataract appeared around three months, which progressed to mature cataract by six months. EPHA2 protein expression in the lens is spatially and temporally regulated. It is low in anterior epithelial cells, upregulated as the cells enter differentiation at the equator, strongly expressed in the cortical fiber cells, but absent in the nuclei. Deletion of Epha2 caused a significant increase in the expression of HSP25 (murine homologue of human HSP27) before the onset of cataract. The overexpressed HSP25 was in an underphosphorylated form, indicating excessive cellular stress and protein misfolding. The orthologous human EPHA2 gene on chromosome 1p36 was tested in three independent worldwide Caucasian populations for allelic association with cortical cataract. Common variants in EPHA2 were found that showed significant association with cortical cataract, and rs6678616 was the most significant in meta-analyses. In addition, we sequenced exons of EPHA2 in linked families and identified a new missense mutation, Arg721Gln, in the protein kinase domain that significantly alters EPHA2 functions in cellular and biochemical assays. Thus, converging evidence from humans and mice suggests that EPHA2 is important in maintaining lens clarity with age.

  20. Telocytes and putative stem cells in ageing human heart.

    PubMed

    Popescu, Laurentiu M; Curici, Antoanela; Wang, Enshi; Zhang, Hao; Hu, Shengshou; Gherghiceanu, Mihaela

    2015-01-01

    Tradition considers that mammalian heart consists of about 70% non-myocytes (interstitial cells) and 30% cardiomyocytes (CMs). Anyway, the presence of telocytes (TCs) has been overlooked, since they were described in 2010 (visit www.telocytes.com). Also, the number of cardiac stem cells (CSCs) has not accurately estimated in humans during ageing. We used electron microscopy to identify and estimate the number of cells in human atrial myocardium (appendages). Three age-related groups were studied: newborns (17 days-1 year), children (6-17 years) and adults (34-60 years). Morphometry was performed on low-magnification electron microscope images using computer-assisted technology. We found that interstitial area gradually increases with age from 31.3 ± 4.9% in newborns to 41 ± 5.2% in adults. Also, the number of blood capillaries (per mm(2) ) increased with several hundreds in children and adults versus newborns. CMs are the most numerous cells, representing 76% in newborns, 88% in children and 86% in adults. Images of CMs mitoses were seen in the 17-day newborns. Interestingly, no lipofuscin granules were found in CMs of human newborns and children. The percentage of cells that occupy interstitium were (depending on age): endothelial cells 52-62%; vascular smooth muscle cells and pericytes 22-28%, Schwann cells with nerve endings 6-7%, fibroblasts 3-10%, macrophages 1-8%, TCs about 1% and stem cells less than 1%. We cannot confirm the popular belief that cardiac fibroblasts are the most prevalent cell type in the heart and account for about 20% of myocardial volume. Numerically, TCs represent a small fraction of human cardiac interstitial cells, but because of their extensive telopodes, they achieve a 3D network that, for instance, supports CSCs. The myocardial (very) low capability to regenerate may be explained by the number of CSCs, which decreases fivefold by age (from 0.5% to 0.1% in newborns versus adults).

  1. Strategies and Challenges in Clinical Trials Targeting Human Aging

    PubMed Central

    Newman, John C.; Milman, Sofiya; Hashmi, Shahrukh K.; Austad, Steve N.; Kirkland, James L.; Halter, Jeffrey B.

    2016-01-01

    Interventions that target fundamental aging processes have the potential to transform human health and health care. A variety of candidate drugs have emerged from basic and translational research that may target aging processes. Some of these drugs are already in clinical use for other purposes, such as metformin and rapamycin. However, designing clinical trials to test interventions that target the aging process poses a unique set of challenges. This paper summarizes the outcomes of an international meeting co-ordinated by the NIH-funded Geroscience Network to further the goal of developing a translational pipeline to move candidate compounds through clinical trials and ultimately into use. We review the evidence that some drugs already in clinical use may target fundamental aging processes. We discuss the design principles of clinical trials to test such interventions in humans, including study populations, interventions, and outcomes. As examples, we offer several scenarios for potential clinical trials centered on the concepts of health span (delayed multimorbidity and functional decline) and resilience (response to or recovery from an acute health stress). Finally, we describe how this discussion helped inform the design of the proposed Targeting Aging with Metformin study. PMID:27535968

  2. Vestibulosympathetic reflex during orthostatic challenge in aging humans

    NASA Technical Reports Server (NTRS)

    Monahan, Kevin D.; Ray, Chester A.

    2002-01-01

    Aging attenuates the increase in muscle sympathetic nerve activity (MSNA) and elicits hypotension during otolith organ engagement in humans. The purpose of the present study was to determine the neural and cardiovascular responses to otolithic engagement during orthostatic stress in older adults. We hypothesized that age-related impairments in the vestibulosympathetic reflex would persist during orthostatic challenge in older subjects and might compromise arterial blood pressure regulation. MSNA, arterial blood pressure, and heart rate responses to head-down rotation (HDR) performed with and without lower body negative pressure (LBNP) in prone subjects were measured. Ten young (27 +/- 1 yr) and 11 older subjects (64 +/- 1 yr) were studied prospectively. HDR performed alone elicited an attenuated increase in MSNA in older subjects (Delta106 +/- 28 vs. Delta20 +/- 7% for young and older subjects). HDR performed during simultaneous orthostatic stress increased total MSNA further in young (Delta53 +/- 15%; P < 0.05) but not older subjects (Delta-5 +/- 4%). Older subjects demonstrated consistent significant hypotension during HDR performed both alone (Delta-6 +/- 2 mmHg) and during LBNP (Delta-7 +/- 2 mmHg). These data provide experimental support for the concept that age-related impairments in the vestibulosympathetic reflex persist during orthostatic challenge in older adults. Furthermore, these findings are consistent with the concept that age-related alterations in vestibular function might contribute to altered orthostatic blood pressure regulation with age in humans.

  3. Thinking Differently About Aging: Changing Attitudes Through the Humanities.

    PubMed

    Marshall, Leni

    2015-08-01

    Ageism has many cumulative negative health effects, so reducing ageism in college-age youths can have a significant, long-term impact on public health. Reduced ageism decreases the prevalence and severity of many negative health events, such as myocardial infarctions, and can add an average of 7.5 years to the life span. One of the few proven methods for reducing ageist ideation is through participation in a video screening and a pair of follow-up conversations. This intervention is similar to the regular activities of many faculty members in the humanities. Gerontologists' expertise with quantitative studies, qualitative studies, and data analysis is needed to determine what factors can improve the efficacy of the intervention and to demonstrate the long-term health impact of specific interventions. Humanities research also will benefit from expanded understandings of aging and old age. Organizations such as the Gerontological Society of America, the European Network in Aging Studies, and the North American Network in Aging Studies can facilitate interdisciplinary collaboration.

  4. Human Respiratory Syncytial Virus: Role of Innate Immunity in Clearance and Disease Progression.

    PubMed

    Farrag, Mohamed A; Almajhdi, Fahad N

    2016-01-01

    Human respiratory syncytial virus (HRSV) infections have worldwide records. The virus is responsible for bronchiolitis, pneumonia, and asthma in humans of different age groups. Premature infants, young children, and immunocompromised individuals are prone to severe HRSV infection that may lead to death. Based on worldwide estimations, millions of cases were reported in both developed and developing countries. In fact, HRSV symptoms develop mainly as a result of host immune response. Due to inability to establish long lasting adaptive immunity, HRSV infection is recurrent and hence impairs vaccine development. Once HRSV attached to the airway epithelia, interaction with the host innate immune components starts. HRSV interaction with pulmonary innate defenses is crucial in determining the disease outcome. Infection of alveolar epithelial cells triggers a cascade of events that lead to recruitment and activation of leukocyte populations. HRSV clearance is mediated by a number of innate leukocytes, including macrophages, natural killer cells, eosinophils, dendritic cells, and neutrophils. Regulation of these cells is mediated by cytokines, chemokines, and other immune mediators. Although the innate immune system helps to clear HRSV infection, it participates in disease progression such as bronchiolitis and asthma. Resolving the mechanisms by which HRSV induces pathogenesis, different possible interactions between the virus and immune components, and immune cells interplay are essential for developing new effective vaccines. Therefore, the current review focuses on how the pulmonary innate defenses mediate HRSV clearance and to what extent they participate in disease progression. In addition, immune responses associated with HRSV vaccines will be discussed.

  5. Recognition and Control of the Progression of Age-Related Hearing Loss

    PubMed Central

    Ren, Hong Miao; Liu, Wei

    2013-01-01

    Abstract Recent breakthroughs have provided notable insights into both the pathogenesis and therapeutic strategies for age-related hearing loss (ARHL). Simultaneously, these breakthroughs enhance our knowledge about this neurodegenerative disease and raise the question of whether the disorder is preventable or even treatable. Discoveries relating to ARHL have revealed a unique link between ARHL and the underlying pathologies. Therefore, we need to better understand the pathogenesis or the mechanism of ARHL and learn how to take full advantage of various therapeutic strategies to prevent the progression of ARHL. PMID:23915327

  6. Age-related decline in prostacyclin synthesis by human aortic endothelial cells. Qualitative and quantitative analysis.

    PubMed Central

    Tokunaga, O.; Yamada, T.; Fan, J. L.; Watanabe, T.

    1991-01-01

    To investigate the functional alteration of human aortic endothelial cells with aging, prostacyclin synthesis was qualitatively and quantitatively examined. The endothelial cells of human aortas and umbilical veins or inferior vena cavae were immunohistochemically examined and found positive for prostacyclin, but the intensity of aortic endothelial cells from older subjects was low. In addition to the endothelial cells, smooth muscle cells in the thickened intima, not the media, of the aorta were also immunoreactive. Endothelial cells were successfully cultured from human aortas obtained from infants through aged subjects and were subdivided into three groups: young, middle, and old. Prostacyclin synthesis by endothelial cells from all types of blood vessels was extremely great at the primary culture, but decreased abruptly in the following subcultures. Among the aortic endothelial cells, the young group synthesized the largest amount of prostacyclin in a conventional culture condition, with synthesis progressively decreasing in the older groups. The in vitro prostacyclin biosynthesis was supported by the qualitative analysis on the tissue sections. These results indicate that prostacyclin synthesis of the aortic endothelial cells decreases with age, but intimal smooth muscle cells potentially have a back-up mechanism and substitute this synthesis to some extent. The decreased synthesis of prostacyclin with age may play an important role in the development and advancement of thrombosis and atherosclerosis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1707240

  7. Lipidomics of human brain aging and Alzheimer's disease pathology.

    PubMed

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context.

  8. Age, Health and Attractiveness Perception of Virtual (Rendered) Human Hair

    PubMed Central

    Fink, Bernhard; Hufschmidt, Carla; Hirn, Thomas; Will, Susanne; McKelvey, Graham; Lankhof, John

    2016-01-01

    The social significance of physical appearance and beauty has been documented in many studies. It is known that even subtle manipulations of facial morphology and skin condition can alter people’s perception of a person’s age, health and attractiveness. While the variation in facial morphology and skin condition cues has been studied quite extensively, comparably little is known on the effect of hair on social perception. This has been partly caused by the technical difficulty of creating appropriate stimuli for investigations of people’s response to systematic variation of certain hair characteristics, such as color and style, while keeping other features constant. Here, we present a modeling approach to the investigation of human hair perception using computer-generated, virtual (rendered) human hair. In three experiments, we manipulated hair diameter (Experiment 1), hair density (Experiment 2), and hair style (Experiment 3) of human (female) head hair and studied perceptions of age, health and attractiveness. Our results show that even subtle changes in these features have an impact on hair perception. We discuss our findings with reference to previous studies on condition-dependent quality cues in women that influence human social perception, thereby suggesting that hair is a salient feature of human physical appearance, which contributes to the perception of beauty. PMID:28066276

  9. Age, Health and Attractiveness Perception of Virtual (Rendered) Human Hair.

    PubMed

    Fink, Bernhard; Hufschmidt, Carla; Hirn, Thomas; Will, Susanne; McKelvey, Graham; Lankhof, John

    2016-01-01

    The social significance of physical appearance and beauty has been documented in many studies. It is known that even subtle manipulations of facial morphology and skin condition can alter people's perception of a person's age, health and attractiveness. While the variation in facial morphology and skin condition cues has been studied quite extensively, comparably little is known on the effect of hair on social perception. This has been partly caused by the technical difficulty of creating appropriate stimuli for investigations of people's response to systematic variation of certain hair characteristics, such as color and style, while keeping other features constant. Here, we present a modeling approach to the investigation of human hair perception using computer-generated, virtual (rendered) human hair. In three experiments, we manipulated hair diameter (Experiment 1), hair density (Experiment 2), and hair style (Experiment 3) of human (female) head hair and studied perceptions of age, health and attractiveness. Our results show that even subtle changes in these features have an impact on hair perception. We discuss our findings with reference to previous studies on condition-dependent quality cues in women that influence human social perception, thereby suggesting that hair is a salient feature of human physical appearance, which contributes to the perception of beauty.

  10. Antioxidant vitamin supplementation for preventing and slowing the progression of age-related cataract

    PubMed Central

    Mathew, Milan C; Ervin, Ann-Margret; Tao, Jeremiah; Davis, Richard M

    2013-01-01

    Background Age-related cataract is a major cause of visual impairment in the elderly. Oxidative stress has been implicated in its formation and progression. Antioxidant vitamin supplementation has been investigated in this context. Objectives To assess the effectiveness of antioxidant vitamin supplementation in preventing and slowing the progression of age-related cataract. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 2), MEDLINE (January 1950 to March 2012), EMBASE (January 1980 to March 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to March 2012), Open Grey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 2 March 2012. We also checked the reference lists of included studies and ongoing trials and contacted investigators to identify eligible randomized trials. Selection criteria We included only randomized controlled trials in which supplementation with one or more antioxidant vitamins (beta-carotene, vitamin C and vitamin E) in any form, dosage or combination for at least one year was compared to another antioxidant vitamin or to placebo. Data collection and analysis Two authors extracted data and assessed trial quality independently. We pooled results for the primary outcomes, i.e., incidence of cataract and incidence of cataract extraction. We did not pool results of the secondary outcomes - progression of cataract and loss of visual acuity, because of differences in definitions of outcomes and data presentation. We pooled results by type of cataract when data

  11. Impact of Aging on Dendritic Cell Functions in humans

    PubMed Central

    Agrawal, Anshu; Gupta, Sudhir

    2010-01-01

    Aging is a paradox of reduced immunity and chronic inflammation. Dendritic cells are central orchestrators of the immune response with a key role in the generation of immunity and maintenance of tolerance. The functions of DCs are compromised with age. There is no major effect on the numbers and phenotype of DC subsets in aged subjects; nevertheless, their capacity to phagocytose antigens and migrate is impaired with age. There is aberrant cytokine secretion by various DC subsets with CDCs secreting increased basal level of pro-inflammatory cytokines but the response on stimulation to foreign antigens is decreased. In contrast, the response to self antigens is increased suggesting erosion of peripheral self tolerance. PDC subset also secretes reduced IFN-alpha in response to viruses. The capacity of DCs to prime T cell responses is also affected. Aging thus has a profound affect on DC functions. Present review summarizes the effect of advancing age on DC functions in humans in the context of both immunity and tolerance. PMID:20619360

  12. Human premature aging, DNA repair and RecQ helicases.

    PubMed

    Brosh, Robert M; Bohr, Vilhelm A

    2007-01-01

    Genomic instability leads to mutations, cellular dysfunction and aberrant phenotypes at the tissue and organism levels. A number of mechanisms have evolved to cope with endogenous or exogenous stress to prevent chromosomal instability and maintain cellular homeostasis. DNA helicases play important roles in the DNA damage response. The RecQ family of DNA helicases is of particular interest since several human RecQ helicases are defective in diseases associated with premature aging and cancer. In this review, we will provide an update on our understanding of the specific roles of human RecQ helicases in the maintenance of genomic stability through their catalytic activities and protein interactions in various pathways of cellular nucleic acid metabolism with an emphasis on DNA replication and repair. We will also discuss the clinical features of the premature aging disorders associated with RecQ helicase deficiencies and how they relate to the molecular defects.

  13. Investigations Into Age-related Changes in the Human Mandible().

    PubMed

    Parr, Nicolette M; Passalacqua, Nicholas V; Skorpinski, Katie

    2017-03-02

    While changes in mandibular shape over time are not widely recognized by skeletal biologists, mandibular remodeling and associated changes in gross morphology may result from a number of causes related to mechanical stress such as antemortem tooth loss, changes in bite force, or alterations of masticatory performance. This study investigated the relationship between age-related changes and antemortem tooth loss in adult humans via dry bone measurements. This study examined 10 standard mandibular measurements as well as individual antemortem tooth loss scores using the Eichner Index from a total of 319 female and male individuals with ages ranging from 16 to 99 years. Results indicate that few mandibular measurements exhibited age-related changes, and most were affected by antemortem tooth loss.

  14. An estrogen-induced endometrial hyperplasia mouse model recapitulating human disease progression and genetic aberrations.

    PubMed

    Yang, Chieh-Hsiang; Almomen, Aliyah; Wee, Yin Shen; Jarboe, Elke A; Peterson, C Matthew; Janát-Amsbury, Margit M

    2015-07-01

    Endometrial hyperplasia (EH) is a condition originating from uterine endometrial glands undergoing disordered proliferation including the risk to progress to endometrial adenocarcinoma. In recent years, a steady increase in EH cases among younger women of reproductive age accentuates the demand of therapeutic alternatives, which emphasizes that an improved disease model for therapeutic agents evaluation is concurrently desired. Here, a new hormone-induced EH mouse model was developed using a subcutaneous estradiol (E2)-sustained releasing pellet, which elevates the serum E2 level in mice, closely mimicking the effect known as estrogen dominance with underlying, pathological E2 levels in patients. The onset and progression of EH generated within this model recapitulate a clinically relevant, pathological transformation, beginning with disordered proliferation developing to simple EH, advancing to atypical EH, and then progressing to precancerous stages, all following a chronologic manner. Although a general increase in nuclear progesterone receptor (PR) expression occurred after E2 expression, a total loss in PR was noted in some endometrial glands as disease advanced to simple EH. Furthermore, estrogen receptor (ER) expression in the nucleus of endometrial cells was reduced in disordered proliferation and increased when EH progressed to atypical EH and precancerous stages. This EH model also resembles other pathological patterns found in human disease such as leukocytic infiltration, genetic aberrations in β-catenin, and joint phosphatase and tensin homolog/paired box gene 2 (PTEN/PAX2) silencing. In summary, this new and comprehensively characterized EH model is cost-effective, easily reproducible, and may serve as a tool for preclinical testing of therapeutic agents and facilitate further investigation of EH.

  15. Mass spectrometry-based proteomic analysis of middle-aged vs. aged vastus lateralis reveals increased levels of carbonic anhydrase isoform 3 in senescent human skeletal muscle.

    PubMed

    Staunton, Lisa; Zweyer, Margit; Swandulla, Dieter; Ohlendieck, Kay

    2012-10-01

    The age-related loss of skeletal muscle mass and associated progressive decline in contractile strength is a serious pathophysiological issue in the elderly. In order to investigate global changes in the skeletal muscle proteome after the fifth decade of life, this study analysed total extracts from human vastus lateralis muscle by fluorescence difference in-gel electrophoresis. Tissue specimens were derived from middle-aged (47-62 years) vs. aged (76-82 years) individuals and potential changes in the protein expression profiles were compared between these two age groups by a comprehensive gel electrophoresis-based survey. Age-dependent alterations in the concentration of 19 protein spots were revealed and mass spectrometry identified these components as being involved in the excitation-contraction-relaxation cycle, muscle metabolism, ion handling and the cellular stress response. This indicates a generally perturbed protein expression pattern in senescent human muscle. Increased levels of mitochondrial enzymes and isoform switching of the key contractile protein, actin, support the idea of glycolytic-to-oxidative and fast-to-slow transition processes during muscle aging. Importantly, the carbonic anhydrase (CA)3 isoform displayed an increased abundance during muscle aging, which was independently verified by immunoblotting of differently aged human skeletal muscle samples. Since the CA3 isoform is relatively muscle-specific and exhibits a fibre type-specific expression pattern, this enzyme may represent an interesting new biomarker of sarcopenia. Increased levels of CA are indicative of an increased demand of CO₂-removal in senescent muscle, and also suggest age-related fibre type shifting to slower-contracting muscles during human aging.

  16. Impact of Age and Myopia on the Rate of Visual Field Progression in Glaucoma Patients.

    PubMed

    Park, Hae-Young Lopilly; Hong, Kyung Euy; Park, Chan Kee

    2016-05-01

    Myopia is rapidly increasing in young populations and patients with glaucoma associated with myopia are reported to be young aged in East Asia. These young patients have a longer life expectancy, which increases their risk of end-of-life visual disabilities. There is a need to understand the clinical course of myopic glaucoma patients, which may be important for the care of these myopic populations. In this study, we evaluated the relationship between the age at presentation and the rate of glaucoma progression in the visual field (VF) according to the presence of myopia. The study was conducted as a prospective observational study including 179 patients with open-angle glaucoma who had undergone at least 5 VF examinations with a follow-up of at least 5 years. The progression rate of the mean deviation (MD) and the pattern standard deviation (PSD) are expressed as change in decibels (dB) per year. The slopes of the MD and PSD were calculated by linear regression analyses. Factors related to the slope of VF MD changes were analyzed with correlation and regression analyses. The slope of the linear fit line plotted against age at presentation and the rate of change in the VF MD was -0.026 (P < 0.001) in the myopic group and -0.008 (P = 0.167) in the nonmyopic group; the relationship was more prominent in the myopic group than the nonmyopic group. In the myopic group, age (β = -0.417; 95% confidence intervals (CI), -0.651 to -0.200; P = 0.050) and baseline untreated intraocular pressure (β = -0.179; 95% CI, -0.331 to -0.028; P = 0.022) were significantly related to the rate of change in the MD, which was only the presence of disc hemorrhage (β = -0.335; 95% CI, -0.568 to -0.018; P = 0.022) in the nonmyopic group. Age at presentation was significantly related to the rate of change in the VF in glaucomatous eyes with myopia compared to eyes without myopia. Older age was significantly related to the rate of change in the VF only in

  17. Human gut microbiome viewed across age and geography.

    PubMed

    Yatsunenko, Tanya; Rey, Federico E; Manary, Mark J; Trehan, Indi; Dominguez-Bello, Maria Gloria; Contreras, Monica; Magris, Magda; Hidalgo, Glida; Baldassano, Robert N; Anokhin, Andrey P; Heath, Andrew C; Warner, Barbara; Reeder, Jens; Kuczynski, Justin; Caporaso, J Gregory; Lozupone, Catherine A; Lauber, Christian; Clemente, Jose Carlos; Knights, Dan; Knight, Rob; Gordon, Jeffrey I

    2012-05-09

    Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization.

  18. Exercise enhances wound healing and prevents cancer progression during aging by targeting macrophage polarity.

    PubMed

    Goh, Jorming; Ladiges, Warren C

    2014-07-01

    Physical activity, which can include regular and repetitive exercise training, has been shown to decrease the incidence of age-related diseases. Aging is characterized by aberrant immune responses, including impaired wound healing and increased cancer risk. The behavior and polarized phenotype of tissue macrophages are distinct between young and old organisms. The balance of M1 and M2 macrophages is altered in the aged tissue microenvironment, with a tilt towards an M2-dominant macrophage population, as well as its associated signaling pathways. These M2-type responses may result in unresolved inflammation and create an environment that impairs wound healing and is favorable for cancer growth. We discuss the concept that exercise training can improve the regulation of macrophage polarization and normalize the inflammatory process, and thereby exert anticancer effects and enhance wound healing in older humans.

  19. Dimethylphosphoryl-inhibited human cholinesterases: inhibition, reactivation, and aging kinetics.

    PubMed

    Worek, F; Diepold, C; Eyer, P

    1999-02-01

    Human poisoning by organophosphates bearing two methoxy groups, e.g. by malathion, paraoxon-methyl, dimethoate and oxydemeton-methyl, is generally considered to be rather resistant to oxime therapy. Since the oxime effectiveness is influenced not only by its reactivating potential but also by inhibition, aging and spontaneous reactivation kinetics, experiments were performed with human acetyl- (AChE) and butyrylcholinesterase (BChE) to determine the respective kinetic constants. The efficacy of obidoxime in reactivating dimethylphosphoryl-AChE was 40, 9 and 3 times higher than of HI 6, pralidoxime and HLö 7, respectively. Aging (t1/2 3.7 h) and spontaneous reactivation (t1/2 0.7 h) occurred concomitantly, with the portion of the aged enzyme being dependent on the presence of excess inhibitor. Calculation of steady-state AChE activity in the presence of inhibitor and oxime revealed that obidoxime was superior to pralidoxime. In addition, organophosphate concentrations up to 10(-6) M (paraoxon-methyl) and 10(-4) M (oxydemeton-methyl) could be counteracted at clinically relevant oxime concentrations (10 microM). These data indicate that oximes may effectively reactivate human dimethylphosphoryl-AChE. Failure of oximes may be attributed to megadose intoxications and to prolonged time intervals between poison uptake and oxime administration. The potency of the oximes to reactivate dimethylphosphoryl-BChE was much lower and the spontaneous reactivation slower (t1/2 9 h), while aging proceeded at a comparable rate. Thus, BChE activity determination for diagnosis and therapeutic monitoring may give no reliable information on AChE status.

  20. Predicting Human Age with Bloodstains by sjTREC Quantification

    PubMed Central

    Wang, Huan; Wang, Hong-sheng; Lu, Hui-ling; Sun, Hong-yu

    2012-01-01

    The age-related decline of signal joint T-cell receptor rearrangement excision circles (sjTRECs) in human peripheral blood has been demonstrated in our previous study and other reports. Until now, only a few studies on sjTREC detection in bloodstain samples were reported, which were based on a small sample of subjects of a limited age range, although bloodstains are much more frequently encountered in forensic practice. In this present study, we adopted the sensitive Taqman real-time quantitative polymerase chain reaction (qPCR) method to perform sjTREC quantification in bloodstains from individuals ranging from 0–86 years old (n = 264). The results revealed that sjTREC contents in human bloodstains were declined in an age-dependent manner (r = −0.8712). The formula of age estimation was Age  = −7.1815Y−42.458±9.42 (Y dCtTBP-sjTREC; 9.42 standard error). Furthermore, we tested for the influence of short- or long- storage time by analyzing fresh and stored bloodstains from the same individuals. Remarkably, no statistically significant difference in sjTREC contents was found between the fresh and old DNA samples over a 4-week of storage time. However, significant loss (0.16–1.93 dCt) in sjTREC contents was detected after 1.5 years of storage in 31 samples. Moreover, preliminary sjTREC quantification from up to 20-year-old bloodstains showed that though the sjTREC contents were detectable in all samples and highly correlated with donor age, a time-dependent decrease in the correlation coefficient r was found, suggesting the predicting accuracy of this described assay would be deteriorated in aged samples. Our findings show that sjTREC quantification might be also suitable for age prediction in bloodstains, and future researches into the time-dependent or other potential impacts on sjTREC quantification might allow further improvement of the predicting accuracy. PMID:22879970

  1. Aging and the reduction in fracture toughness of human dentin.

    PubMed

    Nazari, A; Bajaj, D; Zhang, D; Romberg, E; Arola, D

    2009-10-01

    An evaluation of the crack growth resistance of human coronal dentin was performed on tissue obtained from patients between ages 18 and 83. Stable crack extension was achieved over clinically relevant lengths (0< or = a < or =1mm) under Mode I quasi-static loading and perpendicular to the nominal tubule direction. Results distinguished that human dentin exhibits an increase in crack growth resistance with extension (i.e. rising R-curve) and that there is a significant reduction in both the initiation (K(o)) and plateau (K(p)) components of toughness with patient age. In the young dentin (18< or =age< or =35) there was a 25% increase in the crack growth resistance from the onset of extension (K(o)=1.34 MPa m(0.5)) to the maximum or "plateau" toughness (K(p)=1.65 MPa m(0.5)). In comparison, the crack growth resistance of the old dentin (55< or =age) increased with extension by less than 10% from K(o)=1.08 MPa m(0.5) to K(p)=1.17 MPa m(0.5). In young dentin toughening was achieved by a combination of inelastic deformation of the mineralized collagen matrix and microcracking of the peritubular cuffs. These mechanisms facilitated further toughening via the development of unbroken ligaments of tissue and posterior crack-bridging. Microstructural changes with aging decreased the capacity for near-tip inelastic deformation and microcracking of the tubules, which in turn suppressed the formation of unbroken ligaments and the degree of extrinsic toughening.

  2. Neural Control of the Circulation: How Sex and Age Differences Interact in Humans

    PubMed Central

    Joyner, Michael J.; Barnes, Jill N.; Hart, Emma C.; Wallin, B. Gunnar; Charkoudian, Nisha

    2015-01-01

    The autonomic nervous system is a key regulator of cardiovascular system. In this review we focus on how sex and aging influence autonomic regulation of blood pressure in humans in an effort to understand general issues related to how the autonomic nervous system regulates blood pressure, and the cardiovascular system as a whole. Younger women generally have lower blood pressure and sympathetic activity than younger men. However, both sexes show marked inter-individual variability across age groups with significant overlap seen. Additionally, while men across the lifespan show a clear relationship between markers of whole body sympathetic activity and vascular resistance, such a relationship is not seen in young women. In this context, the ability of the sympathetic nerves to evoke vasoconstriction is lower in young women likely as a result of concurrent β2 mediated vasodilation that offsets α-adrenergic vasoconstriction. These differences reflect both central sympatho-inhibitory effects of estrogen and also its influence on peripheral vasodilation at the level of the vascular smooth muscle and endothelium. By contrast post-menopausal women show a clear relationship between markers of whole body sympathetic traffic and vascular resistance, and sympathetic activity rises progressively in both sexes with aging. These central findings in humans are discussed in the context of differences in population-based trends in blood pressure and orthostatic intolerance. The many areas where there is little sex-specific data on how the autonomic nervous system participates in the regulation of the human cardiovascular system are highlighted. PMID:25589269

  3. 18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression in Caenorhabditis elegans and Neuronal Cultures

    PubMed Central

    Papaevgeniou, Nikoletta; Sakellari, Marianthi; Jha, Sweta; Tavernarakis, Nektarios; Holmberg, Carina I.; Gonos, Efstathios S.

    2016-01-01

    Abstract Aims: Proteasomes are constituents of the cellular proteolytic networks that maintain protein homeostasis through regulated proteolysis of normal and abnormal (in any way) proteins. Genetically mediated proteasome activation in multicellular organisms has been shown to promote longevity and to exert protein antiaggregation activity. In this study, we investigate whether compound-mediated proteasome activation is feasible in a multicellular organism and we dissect the effects of such approach in aging and Alzheimer's disease (AD) progression. Results: Feeding of wild-type Caenorhabditis elegans with 18α-glycyrrhetinic acid (18α-GA; a previously shown proteasome activator in cell culture) results in enhanced levels of proteasome activities that lead to a skinhead-1- and proteasome activation-dependent life span extension. The elevated proteasome function confers lower paralysis rates in various AD nematode models accompanied by decreased Aβ deposits, thus ultimately decelerating the progression of AD phenotype. More importantly, similar positive results are also delivered when human and murine cells of nervous origin are subjected to 18α-GA treatment. Innovation: This is the first report of the use of 18α-GA, a diet-derived compound as prolongevity and antiaggregation factor in the context of a multicellular organism. Conclusion: Our results suggest that proteasome activation with downstream positive outcomes on aging and AD, an aggregation-related disease, is feasible in a nongenetic manipulation manner in a multicellular organism. Moreover, they unveil the need for identification of antiaging and antiamyloidogenic compounds among the nutrients found in our normal diet. Antioxid. Redox Signal. 25, 855–869. PMID:26886723

  4. Sympathetic regulation during thermal stress in human aging and disease

    PubMed Central

    Greaney, Jody L.; Kenney, W. Larry; Alexander, Lacy M.

    2015-01-01

    Humans control their core temperature within a narrow range via precise adjustments of the autonomic nervous system. In response to changing core and/or skin temperature, several critical thermoregulatory reflex effector responses are initiated and include shivering, sweating, and changes in cutaneous blood flow. Cutaneous vasomotor adjustments, mediated by modulations in sympathetic nerve activity (SNA), aid in the maintenance of thermal homeostasis during cold and heat stress since (1) they serve as the first line of defense of body temperature and are initiated before other thermoregulatory effectors, and (2) they are on the efferent arm of non-thermoregulatory reflex systems, aiding in the maintenance of blood pressure and organ perfusion. This review article highlights the sympathetic responses of humans to thermal stress, with a specific focus on primary aging as well as impairments that occur in both heart disease and type 2 diabetes mellitus. Age- and pathology-related changes in efferent muscle and skin SNA during cold and heat stress, measured directly in humans using microneurography, are discussed. PMID:26627337

  5. Reproductive aging patterns in primates reveal that humans are distinct

    PubMed Central

    Alberts, Susan C.; Altmann, Jeanne; Brockman, Diane K.; Cords, Marina; Fedigan, Linda M.; Pusey, Anne; Stoinski, Tara S.; Strier, Karen B.; Morris, William F.; Bronikowski, Anne M.

    2013-01-01

    Women rarely give birth after ∼45 y of age, and they experience the cessation of reproductive cycles, menopause, at ∼50 y of age after a fertility decline lasting almost two decades. Such reproductive senescence in mid-lifespan is an evolutionary puzzle of enduring interest because it should be inherently disadvantageous. Furthermore, comparative data on reproductive senescence from other primates, or indeed other mammals, remains relatively rare. Here we carried out a unique detailed comparative study of reproductive senescence in seven species of nonhuman primates in natural populations, using long-term, individual-based data, and compared them to a population of humans experiencing natural fertility and mortality. In four of seven primate species we found that reproductive senescence occurred before death only in a small minority of individuals. In three primate species we found evidence of reproductive senescence that accelerated throughout adulthood; however, its initial rate was much lower than mortality, so that relatively few individuals experienced reproductive senescence before death. In contrast, the human population showed the predicted and well-known pattern in which reproductive senescence occurred before death for many women and its rate accelerated throughout adulthood. These results provide strong support for the hypothesis that reproductive senescence in midlife, although apparent in natural-fertility, natural-mortality populations of humans, is generally absent in other primates living in such populations. PMID:23898189

  6. Impact Of Human Aging And Modern Lifestyle On Microbiota.

    PubMed

    Valle Gottlieb, Maria Gabriela; Closs, Vera Elizabeth; Junges, Vilma Maria; Schwanke, Carla Helena Augustin

    2017-01-13

    Human evolution and lifestyle changes caused by the agricultural and industrial revolutions have led to great advances in medicine and increased life expectancy, whilst also profoundly altering the ecological relationships and disease patterns of populations. Studies involving populations that still enjoy a rural way of life and with traits similar to the Paleolithic period reveal them to present a more robust, resistant and diverse gut microbiota, in comparison to highly industrialized civilizations. The human diet has expanded and broadened to include the consumption of high-calorie foods, particularly from animal sources such as game, meat and eggs. For some time, the authors have been alert to the fact that a modern lifestyle leads to reduced intake of beneficial bacteria, suggesting that nonpathogenic bacteria are being eradicated. Furthermore, therapeutic procedures, including the use of probiotics and prebiotics, have been proposed to lead to recovery of this microbiota, which is altered due to both the ageing process and lifestyle related aspects. Accordingly, this article aims to review the impact of human aging and modern lifestyle on gut microbiota, within an evolutionary, ecological, epidemiological and therapeutic context.

  7. Progressive outer retinal necrosis: manifestation of human immunodeficiency virus infection.

    PubMed

    Lo, Phey Feng; Lim, Rongxuan; Antonakis, Serafeim N; Almeida, Goncalo C

    2015-05-06

    We present the case of a 54-year-old man who developed progressive outer retinal necrosis (PORN) as an initial manifestation of HIV infection without any significant risk factors for infection with HIV. PORN is usually found as a manifestation of known AIDS late in the disease. Our patient presented with transient visual loss followed by decrease in visual acuity and facial rash. Subsequent investigation revealed anterior chamber tap positive for varicella zoster virus (VZV), as well as HIV positivity, with an initial CD4 count of 48 cells/µL. Systemic and intravitreal antivirals against VZV, and highly active antiretroviral therapy against HIV were started, which halted further progression of retinal necrosis. This case highlights the importance of suspecting PORN where there is a rapidly progressive retinitis, and also testing the patient for HIV, so appropriate treatment can be started.

  8. Progressive neurologic and somatic disease in a novel mouse model of human mucopolysaccharidosis type IIIC

    PubMed Central

    Marcó, Sara; Pujol, Anna; Roca, Carles; Motas, Sandra; Ribera, Albert; Garcia, Miguel; Molas, Maria; Villacampa, Pilar; Melia, Cristian S.; Sánchez, Víctor; Sánchez, Xavier; Bertolin, Joan; Ruberte, Jesús; Haurigot, Virginia

    2016-01-01

    ABSTRACT Mucopolysaccharidosis type IIIC (MPSIIIC) is a severe lysosomal storage disease caused by deficiency in activity of the transmembrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT) that catalyses the N-acetylation of α-glucosamine residues of heparan sulfate. Enzyme deficiency causes abnormal substrate accumulation in lysosomes, leading to progressive and severe neurodegeneration, somatic pathology and early death. There is no cure for MPSIIIC, and development of new therapies is challenging because of the unfeasibility of cross-correction. In this study, we generated a new mouse model of MPSIIIC by targeted disruption of the Hgsnat gene. Successful targeting left LacZ expression under control of the Hgsnat promoter, allowing investigation into sites of endogenous expression, which was particularly prominent in the CNS, but was also detectable in peripheral organs. Signs of CNS storage pathology, including glycosaminoglycan accumulation, lysosomal distension, lysosomal dysfunction and neuroinflammation were detected in 2-month-old animals and progressed with age. Glycosaminoglycan accumulation and ultrastructural changes were also observed in most somatic organs, but lysosomal pathology seemed most severe in liver. Furthermore, HGSNAT-deficient mice had altered locomotor and exploratory activity and shortened lifespan. Hence, this animal model recapitulates human MPSIIIC and provides a useful tool for the study of disease physiopathology and the development of new therapeutic approaches. PMID:27491071

  9. Elastic hysteresis in human eyes is age dependent value.

    PubMed

    Ishii, Kotaro; Saito, Kei; Kameda, Toshihiro; Oshika, Tetsuro

    2012-06-19

    Background:  The elastic hysteresis phenomenon is observed when cyclic loading is applied to a viscoelastic system. The purpose of this study was to quantitatively evaluate elastic hysteresis in living human eyes against an external force. Design:  Prospective case series. Participants:  Twenty-four eyes of 24 normal human subjects (mean age: 41.5 ± 10.6 years) were recruited. Methods:  A non-contact tonometry process was recorded with a high-speed camera. Central corneal thickness (CCT), corneal thickness at 4 mm from the center, corneal curvature, and anterior chamber depth (ACD) were measured. Intraocular pressure (IOP) was also measured using Goldmann applanation tonometry (GAT) and dynamic contour tonometer (DCT). Main Outcome Measures:  Energy loss due to elastic hysteresis was calculated and graphed. Results:  The mean CCT was 552.5 ± 36.1 µm, corneal curvature was 7.84 ± 0.26 mm, and ACD was 2.83 ± 0.29 mm. The mean GAT-IOP was 14.2 ± 2.7 mmHg and DCT-IOP was 16.3 ± 3.5 mmHg. The mean energy loss due to elastic hysteresis was 3.90 × 10(-6) ± 2.49 × 10(-6) Nm. Energy loss due to elastic hysteresis correlated significantly with age (Pearson correlation coefficient = 0.596, p = 0.0016). There were no significant correlations between energy loss due to elastic hysteresis and other measurements. Conclusion:  Energy loss due to elastic hysteresis in the eyes of subjects was found to positively correlate with age, independent of anterior eye structure or IOP. Therefore, it is believed that the viscosity of the eye increases with age. © 2010 The Authors. Clinical and Experimental Ophthalmology © 2010 Royal Australian and New Zealand College of Ophthalmologists.

  10. AGING AND THE REDUCTION IN FRACTURE TOUGHNESS OF HUMAN DENTIN

    PubMed Central

    Nazari, A.; Bajaj, D.; Zhang, D.; Romberg, E.; Arola, D.

    2009-01-01

    An evaluation of the crack growth resistance of human coronal dentin was performed on tissue obtained from patients between ages 18 and 83. Stable crack extension was achieved over clinically relevant lengths (0 ≤ a ≤1 mm) under Mode I quasi-static loading and perpendicular to the nominal tubule direction. Results distinguished that human dentin exhibits an increase in crack growth resistance with extension (i.e. rising R-curve) and that there is a significant reduction in both the initiation (Ko) and plateau (Kp) components of toughness with patient age. In the young dentin (18≤age≤35) there was a 25 % increase in the crack growth resistance from the onset of extension (Ko =1.34 MPa·m0.5) to the maximum or “plateau” toughness (Kp = 1.65 MPa·m0.5). In comparison, the crack growth resistance of the old dentin (55≤age) increased with extension by less than 10 % from Ko = 1.08 MPa·m0.5 to Kp = 1.17 MPa·m0.5. In young dentin toughening was achieved by a combination of inelastic deformation of the mineralized collagen matrix and microcracking of the peritubular cuffs. These mechanisms facilitated further toughening via the development of unbroken ligaments of tissue and posterior crack-bridging. Microstructural changes with aging decreased the capacity for near-tip inelastic deformation and microcracking of the tubules, which in turn suppressed the formation of unbroken ligaments and the degree of extrinsic toughening. PMID:19627862

  11. Raman spectroscopy of human skin: looking for a quantitative algorithm to reliably estimate human age

    NASA Astrophysics Data System (ADS)

    Pezzotti, Giuseppe; Boffelli, Marco; Miyamori, Daisuke; Uemura, Takeshi; Marunaka, Yoshinori; Zhu, Wenliang; Ikegaya, Hiroshi

    2015-06-01

    The possibility of examining soft tissues by Raman spectroscopy is challenged in an attempt to probe human age for the changes in biochemical composition of skin that accompany aging. We present a proof-of-concept report for explicating the biophysical links between vibrational characteristics and the specific compositional and chemical changes associated with aging. The actual existence of such links is then phenomenologically proved. In an attempt to foster the basics for a quantitative use of Raman spectroscopy in assessing aging from human skin samples, a precise spectral deconvolution is performed as a function of donors' ages on five cadaveric samples, which emphasizes the physical significance and the morphological modifications of the Raman bands. The outputs suggest the presence of spectral markers for age identification from skin samples. Some of them appeared as authentic "biological clocks" for the apparent exactness with which they are related to age. Our spectroscopic approach yields clear compositional information of protein folding and crystallization of lipid structures, which can lead to a precise identification of age from infants to adults. Once statistically validated, these parameters might be used to link vibrational aspects at the molecular scale for practical forensic purposes.

  12. [Rheumatoid factor activity, age at manifestation and roentgenologic progression of rheumatoid arthritis--a retrospective study].

    PubMed

    Hein, G; Eidner, G; Eidner, T; Marzoll, I; Klinner, M

    1993-01-01

    The outcome of RF-activity (measured by hemagglutination in the modification of Podliachouk-Harboe) was investigated in 95 patients with RA. In 52 of these patients the radiological progression (modification of Larsen index for hands and feet) in correlation to the outcome of RF was assessed. The results can be summarized in the following way: 1. Elderly RA patients show a significant elevation of RF titer. 2. There is a statistically insignificant correlation between age of RA manifestation and RF level. 3. The investigation of individual RF outcome shows that 54% of the patients have a relatively constant RF level, 15% tend to a decrease of the level of RF activity. Increased RF activity could only be demonstrated in 31% of the patients in the follow-up. 4. We more often observed a decrease of RF activity in RA cases with a disease manifestation < 30 y. We found no significant decrease in the follow-up in cases with manifestation > 60 y. 5. RA patients with a high level of RF activity (HAR > 1:512) have a significantly higher radiological progression index than cases with a low RF activity (HAR < 1:512).

  13. Progress and challenges in probing the human brain.

    PubMed

    Poldrack, Russell A; Farah, Martha J

    2015-10-15

    Perhaps one of the greatest scientific challenges is to understand the human brain. Here we review current methods in human neuroscience, highlighting the ways that they have been used to study the neural bases of the human mind. We begin with a consideration of different levels of description relevant to human neuroscience, from molecules to large-scale networks, and then review the methods that probe these levels and the ability of these methods to test hypotheses about causal mechanisms. Functional MRI is considered in particular detail, as it has been responsible for much of the recent growth of human neuroscience research. We briefly review its inferential strengths and weaknesses and present examples of new analytic approaches that allow inferences beyond simple localization of psychological processes. Finally, we review the prospects for real-world applications and new scientific challenges for human neuroscience.

  14. The Biology of Aging: Citizen Scientists and Their Pets as a Bridge Between Research on Model Organisms and Human Subjects.

    PubMed

    Kaeberlein, M

    2016-03-01

    A fundamental goal of research into the basic mechanisms of aging is to develop translational strategies that improve human health by delaying the onset and progression of age-related pathology. Several interventions have been discovered that increase life span in invertebrate organisms, some of which have similar effects in mice. These include dietary restriction and inhibition of the mechanistic target of rapamycin by treatment with rapamycin. Key challenges moving forward will be to assess the extent to which these and other interventions improve healthy longevity and increase life span in mice and to develop practical strategies for extending this work to the clinic. Companion animals may provide an optimal intermediate between laboratory models and humans. By improving healthy longevity in companion animals, important insights will be gained regarding human aging while improving the quality of life for people and their pets.

  15. The biology of aging: citizen scientists and their pets as a bridge between research on model organisms and human subjects

    PubMed Central

    Kaeberlein, Matt

    2016-01-01

    A fundamental goal of research into the basic mechanisms of aging is to develop translational strategies that improve human health by delaying the onset and progression of age-related pathology. Several interventions have been discovered that increase lifespan in invertebrate organisms, some of which have similar effects in mice. These include dietary restriction and inhibition of the mechanistic target of rapamycin by treatment with rapamycin. Key challenges moving forward will be to assess the extent to which these and other interventions improve healthy longevity in addition to increasing lifespan in mice, and to develop practical strategies for extending this work to the clinic. Companion animals may provide an optimal intermediate between laboratory models and humans. By improving healthy longevity in companion animals, important insights will be gained regarding human aging while simultaneously improving quality of life for people and their pets. PMID:26077786

  16. Environmental carcinogens in human target tissues in culture. Progress report

    SciTech Connect

    Hsu, I.C.

    1986-02-19

    Cells from different organ or animal species have shown diverse activities in activation and detoxification of chemical carcinogens. Based on the mutation assays, human hepatocytes were more effective than animal hepatocytes in detoxification of aromatic nitrogen compounds. The adduct formation was also different in human and rodent hepatocytes exposed to aminofluorene (AF) or acetylaminofluorene (AAF). Both AF and AAF adduct DNA were observed in rat liver cells exposed to AF or AAF. However, very little acetylation or deacetyl of the DNA adducts occurred in the human hepatocytes. Human hepatocytes treated with AF in primary culture produced mainly AF adducted DNA while AAF treated cells formed AAF adduct DNA. 2 figs., 1 tab.

  17. Age and Smoking Related Changes in Metal Ion Levels in Human Lens: Implications for Cataract Formation.

    PubMed

    Langford-Smith, Alex; Tilakaratna, Viranga; Lythgoe, Paul R; Clark, Simon J; Bishop, Paul N; Day, Anthony J

    2016-01-01

    Age-related cataract formation is the primary cause of blindness worldwide and although treatable by surgical removal of the lens the majority of sufferers have neither the finances nor access to the medical facilities required. Therefore, a better understanding of the pathogenesis of cataract may identify new therapeutic targets to prevent or slow its progression. Cataract incidence is strongly correlated with age and cigarette smoking, factors that are often associated with accumulation of metal ions in other tissues. Therefore this study evaluated the age-related changes in 14 metal ions in 32 post mortem human lenses without known cataract from donors of 11 to 82 years of age by inductively coupled plasma mass spectrometry; smoking-related changes in 10 smokers verses 14 non-smokers were also analysed. A significant age-related increase in selenium and decrease in copper ions was observed for the first time in the lens tissue, where cadmium ion levels were also increased as has been seen previously. Aluminium and vanadium ions were found to be increased in smokers compared to non-smokers (an analysis that has only been carried out before in lenses with cataract). These changes in metal ions, i.e. that occur as a consequence of normal ageing and of smoking, could contribute to cataract formation via induction of oxidative stress pathways, modulation of extracellular matrix structure/function and cellular toxicity. Thus, this study has identified novel changes in metal ions in human lens that could potentially drive the pathology of cataract formation.

  18. Age and Smoking Related Changes in Metal Ion Levels in Human Lens: Implications for Cataract Formation

    PubMed Central

    Langford-Smith, Alex; Tilakaratna, Viranga; Lythgoe, Paul R.; Clark, Simon J.; Bishop, Paul N.; Day, Anthony J.

    2016-01-01

    Age-related cataract formation is the primary cause of blindness worldwide and although treatable by surgical removal of the lens the majority of sufferers have neither the finances nor access to the medical facilities required. Therefore, a better understanding of the pathogenesis of cataract may identify new therapeutic targets to prevent or slow its progression. Cataract incidence is strongly correlated with age and cigarette smoking, factors that are often associated with accumulation of metal ions in other tissues. Therefore this study evaluated the age-related changes in 14 metal ions in 32 post mortem human lenses without known cataract from donors of 11 to 82 years of age by inductively coupled plasma mass spectrometry; smoking-related changes in 10 smokers verses 14 non-smokers were also analysed. A significant age-related increase in selenium and decrease in copper ions was observed for the first time in the lens tissue, where cadmium ion levels were also increased as has been seen previously. Aluminium and vanadium ions were found to be increased in smokers compared to non-smokers (an analysis that has only been carried out before in lenses with cataract). These changes in metal ions, i.e. that occur as a consequence of normal ageing and of smoking, could contribute to cataract formation via induction of oxidative stress pathways, modulation of extracellular matrix structure/function and cellular toxicity. Thus, this study has identified novel changes in metal ions in human lens that could potentially drive the pathology of cataract formation. PMID:26794210

  19. Gut Bifidobacteria Populations in Human Health and Aging

    PubMed Central

    Arboleya, Silvia; Watkins, Claire; Stanton, Catherine; Ross, R. Paul

    2016-01-01

    The intestinal microbiota has increasingly been shown to have a vital role in various aspects of human health. Indeed, several studies have linked alterations in the gut microbiota with the development of different diseases. Among the vast gut bacterial community, Bifidobacterium is a genus which dominates the intestine of healthy breast-fed infants whereas in adulthood the levels are lower but relatively stable. The presence of different species of bifidobacteria changes with age, from childhood to old age. Bifidobacterium longum, B. breve, and B. bifidum are generally dominant in infants, whereas B. catenulatum, B. adolescentis and, as well as B. longum are more prevalent in adults. Increasingly, evidence is accumulating which shows beneficial effects of supplementation with bifidobacteria for the improvement of human health conditions ranging from protection against infection to different extra- and intra-intestinal positive effects. Moreover, bifidobacteria have been associated with the production of a number of potentially health promoting metabolites including short chain fatty acids, conjugated linoleic acid and bacteriocins. The aim of this mini-review is to describe the bifidobacteria compositional changes associated with different stages in life, highlighting their beneficial role, as well as their presence or absence in many disease states. PMID:27594848

  20. Gut Bifidobacteria Populations in Human Health and Aging.

    PubMed

    Arboleya, Silvia; Watkins, Claire; Stanton, Catherine; Ross, R Paul

    2016-01-01

    The intestinal microbiota has increasingly been shown to have a vital role in various aspects of human health. Indeed, several studies have linked alterations in the gut microbiota with the development of different diseases. Among the vast gut bacterial community, Bifidobacterium is a genus which dominates the intestine of healthy breast-fed infants whereas in adulthood the levels are lower but relatively stable. The presence of different species of bifidobacteria changes with age, from childhood to old age. Bifidobacterium longum, B. breve, and B. bifidum are generally dominant in infants, whereas B. catenulatum, B. adolescentis and, as well as B. longum are more prevalent in adults. Increasingly, evidence is accumulating which shows beneficial effects of supplementation with bifidobacteria for the improvement of human health conditions ranging from protection against infection to different extra- and intra-intestinal positive effects. Moreover, bifidobacteria have been associated with the production of a number of potentially health promoting metabolites including short chain fatty acids, conjugated linoleic acid and bacteriocins. The aim of this mini-review is to describe the bifidobacteria compositional changes associated with different stages in life, highlighting their beneficial role, as well as their presence or absence in many disease states.

  1. Age-related characteristics of risky decision-making and progressive expectation formation.

    PubMed

    Kardos, Zsófia; Kóbor, Andrea; Takács, Ádám; Tóth, Brigitta; Boha, Roland; File, Bálint; Molnár, Márk

    2016-10-01

    During daily encounters, it is inevitable that people take risks. Investigating the sequential processing of risk hazards involve expectation formation about outcome contingencies. The present study aimed to explore risk behavior and its neural correlates in sequences of decision making, particularly in old age, which represents a critical period regarding risk-taking propensity. The Balloon Analogue Risk Task was used in an electrophysiological setting with young and elderly age groups. During the task each additional pump on a virtual balloon increased the likelihood of a balloon burst but also increased the chance to collect more reward. Event-related potentials associated with rewarding feedback were analyzed based on the forthcoming decisions (whether to continue or to stop) in order to differentiate between states of expectation towards gain or loss. In the young, the reward positivity ERP component increased as a function of reward contingencies with the largest amplitude for rewarding feedback followed by the decision to stop. In the elderly, however, reward positivity did not reflect the effect of reward structure. Behavioral indices of risk-taking propensity suggest that the performance of the young and the elderly were dissociable only with respect to response times: The elderly was characterized by hesitation and more deliberative decision making throughout the experiment. These findings signify that sequential tracking of outcome contingencies has a key role in cost-efficient action planning and progressive expectation formation.

  2. Aging of microstructural compartments in human compact bone

    NASA Technical Reports Server (NTRS)

    Akkus, Ozan; Polyakova-Akkus, Anna; Adar, Fran; Schaffler, Mitchell B.

    2003-01-01

    Composition of microstructural compartments in compact bone of aging male subjects was assessed using Raman microscopy. Secondary mineralization of unremodeled fragments persisted for two decades. Replacement of these tissue fragments with secondary osteons kept mean composition constant over age, but at a fully mineralized limit. Slowing of remodeling may increase fracture susceptibility through an increase in proportion of highly mineralized tissue. In this study, the aging process in the microstructural compartments of human femoral cortical bone was investigated and related to changes in the overall tissue composition within the age range of 17-73 years. Raman microprobe analysis was used to assess the mineral content, mineral crystallinity, and carbonate substitution in fragments of primary lamellar bone that survived remodeling for decades. Tissue composition of the secondary osteonal population was investigated to determine the composition of turned over tissue volume. Finally, Raman spectral analysis of homogenized tissue was performed to evaluate the effects of unremodeled and newly formed tissue on the overall tissue composition. The chemical composition of the primary lamellar bone exhibited two chronological stages. Organic matrix became more mineralized and the crystallinity of the mineral improved during the first stage, which lasted for two decades. The mineral content and the mineral crystallinity did not vary during the second stage. The results for the primary lamellar bone demonstrated that physiological mineralization, as evidenced by crystal growth and maturation, is a continuous process that may persist as long as two decades, and the growth and maturation process stops after the organic matrix becomes "fully mineralized." The average mineral content and the average mineral crystallinity of the homogenized tissue did not change with age. It was also observed that the mineral content of the homogenized tissue was consistently greater than the

  3. Human Health and Support Systems Capability Roadmap Progress Review

    NASA Technical Reports Server (NTRS)

    Grounds, Dennis; Boehm, Al

    2005-01-01

    The Human Health and Support Systems Capability Roadmap focuses on research and technology development and demonstration required to ensure the health, habitation, safety, and effectiveness of crews in and beyond low Earth orbit. It contains three distinct sub-capabilities: Human Health and Performance. Life Support and Habitats. Extra-Vehicular Activity.

  4. Human liver proteome project: plan, progress, and perspectives.

    PubMed

    He, Fuchu

    2005-12-01

    The Human Liver Proteome Project is the first initiative of the human proteome project for human organs/tissues and aims at writing a modern Prometheus myth. Its global scientific objectives are to reveal the "solar system" of the human liver proteome, expression profiles, modification profiles, a protein linkage (protein-protein interaction) map, and a proteome localization map, and to define an ORFeome, physiome, and pathome. Since it was first proposed in April 2002, the Human Liver Proteome Project has attracted more than 100 laboratories from all over the world. In the ensuing 3 years, we set up a management infrastructure, identified reference laboratories, confirmed standard operating procedures, initiated international research collaborations, and finally achieved the first set of expression profile data.

  5. Twins for epigenetic studies of human aging and development.

    PubMed

    Tan, Qihua; Christiansen, Lene; Thomassen, Mads; Kruse, Torben A; Christensen, Kaare

    2013-01-01

    Most of the complex traits including aging phenotypes are caused by the interaction between genome and environmental conditions and the interface of epigenetics may be a central mechanism. Although modern technologies allow us high-throughput profiling of epigenetic patterns already at genome level, our understanding of genetic and environmental influences on the epigenetic processes remains limited. Twins are of special interest for genetic studies due to their genetic similarity and rearing-environment sharing. The classical twin design has made a great contribution in dissecting the genetic and environmental contributions to human diseases and complex traits. In the era of functional genomics, the valuable sample of twins is helping to bridge the gap between gene activity and the environments through epigenetic mechanisms unlimited by DNA sequence variations. We propose to extend the classical twin design to study the aging-related molecular epigenetic phenotypes and link them with environmental exposures especially early life events. Different study designs and application issues will be highlighted and novel approaches introduced with aim at making uses of twins in assessing the environmental impact on epigenetic changes during development and in the aging process.

  6. Maladaptive bias for extrahippocampal navigation strategies in aging humans.

    PubMed

    Wiener, Jan M; de Condappa, Olivier; Harris, Mathew A; Wolbers, Thomas

    2013-04-03

    Efficient spatial navigation requires not only accurate spatial knowledge but also the selection of appropriate strategies. Using a novel paradigm that allowed us to distinguish between beacon, associative cue, and place strategies, we investigated the effects of cognitive aging on the selection and adoption of navigation strategies in humans. Participants were required to rejoin a previously learned route encountered from an unfamiliar direction. Successful performance required the use of an allocentric place strategy, which was increasingly observed in young participants over six experimental sessions. In contrast, older participants, who were able to recall the route when approaching intersections from the same direction as during encoding, failed to use the correct place strategy when approaching intersections from novel directions. Instead, they continuously used a beacon strategy and showed no evidence of changing their behavior across the six sessions. Given that this bias was already apparent in the first experimental session, the inability to adopt the correct place strategy is not related to an inability to switch from a firmly established response strategy to an allocentric place strategy. Rather, and in line with previous research, age-related deficits in allocentric processing result in shifts in preferred navigation strategies and an overall bias for response strategies. The specific preference for a beacon strategy is discussed in the context of a possible dissociation between beacon-based and associative-cue-based response learning in the striatum, with the latter being more sensitive to age-related changes.

  7. Mitochondrial-Nuclear Epistasis: Implications for Human Aging and Longevity

    PubMed Central

    Tranah, Gregory

    2010-01-01

    There is substantial evidence that mitochondria are involved in the aging process. Mitochondrial function requires the coordinated expression of hundreds of nuclear genes and a few dozen mitochondrial genes, many of which have been associated with either extended or shortened life span. Impaired mitochondrial function resulting from mtDNA and nuclear DNA variation is likely to contribute to an imbalance in cellular energy homeostasis, increased vulnerability to oxidative stress, and an increased rate of cellular senescence and aging. The complex genetic architecture of mitochondria suggests that there may be an equally complex set of gene interactions (epistases) involving genetic variation in the nuclear and mitochondrial genomes. Results from Drosophila suggest that the effects of mtDNA haplotypes on longevity vary among different nuclear allelic backgrounds, which could account for the inconsistent associations that have been observed between mitochondrial DNA (mtDNA) haplogroups and survival in humans. A diversity of pathways may influence the way mitochondria and nuclear – mitochondrial interactions modulate longevity, including: oxidative phosphorylation; mitochondrial uncoupling; antioxidant defenses; mitochondrial fission and fusion; and sirtuin regulation of mitochondrial genes. We hypothesize that aging and longevity, as complex traits having a significant genetic component, are likely to be controlled by nuclear gene variants interacting with both inherited and somatic mtDNA variability. PMID:20601194

  8. Catalog of genetic progression of human cancers: breast cancer.

    PubMed

    Desmedt, Christine; Yates, Lucy; Kulka, Janina

    2016-03-01

    With the rapid development of next-generation sequencing, deeper insights are being gained into the molecular evolution that underlies the development and clinical progression of breast cancer. It is apparent that during evolution, breast cancers acquire thousands of mutations including single base pair substitutions, insertions, deletions, copy number aberrations, and structural rearrangements. As a consequence, at the whole genome level, no two cancers are identical and few cancers even share the same complement of "driver" mutations. Indeed, two samples from the same cancer may also exhibit extensive differences due to constant remodeling of the genome over time. In this review, we summarize recent studies that extend our understanding of the genomic basis of cancer progression. Key biological insights include the following: subclonal diversification begins early in cancer evolution, being detectable even in in situ lesions; geographical stratification of subclonal structure is frequent in primary tumors and can include therapeutically targetable alterations; multiple distant metastases typically arise from a common metastatic ancestor following a "metastatic cascade" model; systemic therapy can unmask preexisting resistant subclones or influence further treatment sensitivity and disease progression. We conclude the review by describing novel approaches such as the analysis of circulating DNA and patient-derived xenografts that promise to further our understanding of the genomic changes occurring during cancer evolution and guide treatment decision making.

  9. Aging and Fracture of Human Cortical Bone and Tooth Dentin

    SciTech Connect

    Ager, Joel; Koester, Kurt J.; Ager III, Joel W.; Ritchie, Robert O.

    2008-05-07

    Mineralized tissues, such as bone and tooth dentin, serve as structural materials in the human body and, as such, have evolved to resist fracture. In assessing their quantitative fracture resistance or toughness, it is important to distinguish between intrinsic toughening mechanisms which function ahead of the crack tip, such as plasticity in metals, and extrinsic mechanisms which function primarily behind the tip, such as crack bridging in ceramics. Bone and dentin derive their resistance to fracture principally from extrinsic toughening mechanisms which have their origins in the hierarchical microstructure of these mineralized tissues. Experimentally, quantification of these toughening mechanisms requires a crack-growth resistance approach, which can be achieved by measuring the crack-driving force, e.g., the stress intensity, as a function of crack extension ("R-curve approach"). Here this methodology is used to study of the effect of aging on the fracture properties of human cortical bone and human dentin in order to discern the microstructural origins of toughness in these materials.

  10. Aging and fracture of human cortical bone and tooth dentin

    NASA Astrophysics Data System (ADS)

    Koester, Kurt J.; Ager, Joel W.; Ritchie, Robert O.

    2008-06-01

    Mineralized tissues, such as bone and tooth dentin, serve as structural materials in the human body and, as such, have evolved to resist fracture. In assessing their quantitative fracture resistance or toughness, it is important to distinguish between intrinsic toughening mechanisms, which function ahead of the crack tip, such as plasticity in metals, and extrinsic mechanisms, which function primarily behind the tip, such as crack bridging in ceramics. Bone and dentin derive their resistance to fracture principally from extrinsic toughening mechanisms, which have their origins in the hierarchical microstructure of these mineralized tissues. Experimentally, quantification of these toughening mechanisms requires a crack-growth resistance approach, which can be achieved by measuring the crack-driving force (e.g., the stress intensity) as a function of crack extension (“R-curve approach”). Here this methodology is used to study the effect of aging on the fracture properties of human cortical bone and human dentin in order to discern the microstructural origins of toughness in these materials.

  11. Age-associated changes in rich-club organisation in autistic and neurotypical human brains

    PubMed Central

    Watanabe, Takamitsu; Rees, Geraint

    2015-01-01

    Macroscopic structural networks in the human brain have a rich-club architecture comprising both highly inter-connected central regions and sparsely connected peripheral regions. Recent studies show that disruption of this functionally efficient organisation is associated with several psychiatric disorders. However, despite increasing attention to this network property, whether age-associated changes in rich-club organisation occur during human adolescence remains unclear. Here, analysing a publicly shared diffusion tensor imaging dataset, we found that, during adolescence, brains of typically developing (TD) individuals showed increases in rich-club organisation and inferred network functionality, whereas individuals with autism spectrum disorders (ASD) did not. These differences between TD and ASD groups were statistically significant for both structural and functional properties. Moreover, this typical age-related changes in rich-club organisation were characterised by progressive involvement of the right anterior insula. In contrast, in ASD individuals, did not show typical increases in grey matter volume, and this relative anatomical immaturity was correlated with the severity of ASD social symptoms. These results provide evidence that rich-club architecture is one of the bases of functionally efficient brain networks underpinning complex cognitive functions in adult human brains. Furthermore, our findings suggest that immature rich-club organisation might be associated with some neurodevelopmental disorders. PMID:26537477

  12. Metabolomics of human brain aging and age-related neurodegenerative diseases.

    PubMed

    Jové, Mariona; Portero-Otín, Manuel; Naudí, Alba; Ferrer, Isidre; Pamplona, Reinald

    2014-07-01

    Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.

  13. Progress in coupling models of human and coastal landscape change

    NASA Astrophysics Data System (ADS)

    Brad Murray, A.; Gopalakrishnan, Sathya; McNamara, Dylan E.; Smith, Martin D.

    2013-04-01

    Humans are increasingly altering the Earth's surface, and affecting processes that shape and reshape landscapes. In many cases, humans are reacting to landscape-change processes that represent natural hazards. Thus, the landscape is reacting to humans who are reacting to the landscape. When the timescales for landscape change are comparable to those of human dynamics, human and 'natural' components of developed environments are dynamically coupled—necessitating coupling models of human and physical/biological processes to study either environmental change or human responses. Here we focus on a case study coupling models of coastal economics and physical coastline change. In this modeling, coastline change results from patterns of wave-driven sediment transport and sea-level rise, and shoreline stabilization decisions are based on the benefits of wide beaches (capitalized into property values) balanced against the costs of stabilization. This interdisciplinary modeling highlights points that may apply to other coupled human/natural systems. First, climate change, by accelerating the rates of landscape change, tends to strengthen the coupling with human dynamics. In our case study, both increasing sea-level-rise rates and changing storm patterns tend to increase shoreline change rates, which can induce more vigorous shoreline stabilization efforts. However, property values can fall dramatically as erosion rates and stabilization costs rise, which can also lead to the abandonment of expensive stabilization methods as shoreline change rates increase. Second, socio-economic change can also strengthen the human/landscape coupling. Changing costs of shoreline stabilization can alter stabilization decisions, which in turn alters patterns of coastline change. The coupled modeling illuminates the long-range effects of localized shoreline stabilization efforts; communities arrayed along a coastline are unwittingly affecting each other's erosion rates, and therefore each

  14. Research on human genetics in Iceland. Progress report

    SciTech Connect

    1980-10-31

    Records of the Icelandic Population are being used to investigate the possible inheritance of disabilities and diseases as well as other characters and the effect of environment on man. The progress report of research covers the period 1977 to 1980. The investigation was begun in 1965 by the Genetical Committee of the University of Iceland and the materials used are demographic records from the year 1840 to present and various medical information. The records are being computerized and linked together to make them effective for use in hereditary studies.

  15. Progress report on research on human genetics in Iceland

    SciTech Connect

    1980-10-31

    Records of the Icelandic population are being used to investigate the possible inheritance of disabilities and diseases as well as other characteristics and the effect of environment on man. The progress report of research covers the period from 1977 to 1980. The investigation was begun in 1965 by the Genetical Committee of the University of Iceland and the materials used are demographic records from the year 1840 to present and various medical information. The records are being computerized and linked together to make them effective for use in hereditary studies.

  16. Ventriculomegaly associated with ependymal gliosis and declines in barrier integrity in the aging human and mouse brain

    PubMed Central

    Shook, Brett A; Lennington, Jessica B; Acabchuk, Rebecca L; Halling, Meredith; Sun, Ye; Peters, John; Wu, Qian; Mahajan, Amit; Fellows, Douglas W; Conover, Joanne C

    2014-01-01

    Age-associated ventriculomegaly is typically attributed to neurodegeneration; however, additional factors might initiate or contribute to progressive ventricular expansion. By directly linking postmortem human MRI sequences with histological features of periventricular tissue, we show that substantial lateral ventricle surface gliosis is associated with ventriculomegaly. To examine whether loss of ependymal cell coverage resulting in ventricle surface glial scarring can lead directly to ventricle enlargement independent of any other injury or degenerative loss, we modeled in mice the glial scarring found along the lateral ventricle surface in aged humans. Neuraminidase, which cleaves glycosidic linkages of apical adherens junction proteins, was administered intracerebroventricularly to denude areas of ependymal cells. Substantial ependymal cell loss resulted in reactive gliosis rather than stem cell-mediated regenerative repair of the ventricle lining, and the gliotic regions showed morphologic and phenotypic characteristics similar to those found in aged humans. Increased levels of aquaporin-4, indicative of edema, observed in regions of periventricular gliosis in human tissue were also replicated in our mouse model. 3D modeling together with volume measurements revealed that mice with ventricle surface scarring developed expanded ventricles, independent of neurodegeneration. Through a comprehensive, comparative analysis of the lateral ventricles and associated periventricular tissue in aged humans and mouse, followed by modeling of surface gliosis in mice, we have demonstrated a direct link between lateral ventricle surface gliosis and ventricle enlargement. These studies highlight the importance of maintaining an intact ependymal cell lining throughout aging. PMID:24341850

  17. Ventriculomegaly associated with ependymal gliosis and declines in barrier integrity in the aging human and mouse brain.

    PubMed

    Shook, Brett A; Lennington, Jessica B; Acabchuk, Rebecca L; Halling, Meredith; Sun, Ye; Peters, John; Wu, Qian; Mahajan, Amit; Fellows, Douglas W; Conover, Joanne C

    2014-04-01

    Age-associated ventriculomegaly is typically attributed to neurodegeneration; however, additional factors might initiate or contribute to progressive ventricular expansion. By directly linking postmortem human MRI sequences with histological features of periventricular tissue, we show that substantial lateral ventricle surface gliosis is associated with ventriculomegaly. To examine whether loss of ependymal cell coverage resulting in ventricle surface glial scarring can lead directly to ventricle enlargement independent of any other injury or degenerative loss, we modeled in mice the glial scarring found along the lateral ventricle surface in aged humans. Neuraminidase, which cleaves glycosidic linkages of apical adherens junction proteins, was administered intracerebroventricularly to denude areas of ependymal cells. Substantial ependymal cell loss resulted in reactive gliosis rather than stem cell-mediated regenerative repair of the ventricle lining, and the gliotic regions showed morphologic and phenotypic characteristics similar to those found in aged humans. Increased levels of aquaporin-4, indicative of edema, observed in regions of periventricular gliosis in human tissue were also replicated in our mouse model. 3D modeling together with volume measurements revealed that mice with ventricle surface scarring developed expanded ventricles, independent of neurodegeneration. Through a comprehensive, comparative analysis of the lateral ventricles and associated periventricular tissue in aged humans and mouse, followed by modeling of surface gliosis in mice, we have demonstrated a direct link between lateral ventricle surface gliosis and ventricle enlargement. These studies highlight the importance of maintaining an intact ependymal cell lining throughout aging.

  18. Valuable human capital: the aging health care worker.

    PubMed

    Collins, Sandra K; Collins, Kevin S

    2006-01-01

    With the workforce growing older and the supply of younger workers diminishing, it is critical for health care managers to understand the factors necessary to capitalize on their vintage employees. Retaining this segment of the workforce has a multitude of benefits including the preservation of valuable intellectual capital, which is necessary to ensure that health care organizations maintain their competitive advantage in the consumer-driven market. Retaining the aging employee is possible if health care managers learn the motivators and training differences associated with this category of the workforce. These employees should be considered a valuable resource of human capital because without their extensive expertise, intense loyalty and work ethic, and superior customer service skills, health care organizations could suffer severe economic repercussions in the near future.

  19. Fourth international workshop on human chromosome 5. Final progress report

    SciTech Connect

    McPherson, J.D.

    1996-12-31

    The Fourth International Workshop on Human Chromosome 5 was held in Manchester, UK on November 9--10, 1996 and was hosted by the University of Manchester. The major goals of the workshop were: (1) to collate the various genetic, cytogenetic and physical maps of human chromosome 5; (2) to integrate these maps and identify/correct discrepancies between them wherever possible; (3) to catalogue the sequence-ready contigs of the chromosome; (4) to co-ordinate the various sequencing efforts to avoid future duplication; (5) to establish the first (to the author`s knowledge) web site for the human chromosome 5 community which contains the above information in a readily accessible form.

  20. Age-Dependent Changes in Pb Concentration in Human Teeth.

    PubMed

    Fischer, Agnieszka; Wiechuła, Danuta

    2016-09-01

    The result of exposure to Pb is its accumulation in mineralized tissues. In human body, they constitute a reservoir of approx. 90 % of the Pb reserve. The conducted research aimed at determining the accumulation of Pb in calcified tissues of permanent teeth. The concentration of Pb in 390 samples of teeth taken from a selected group of Polish people was determined using the AAS method. Average concentration of Pb in teeth amounted to 14.3 ± 8.18 μg/g, range of changes: 2.21-54.8 μgPb/g. Accumulation of Pb in human body was determined based on changes in Pb concentration in teeth of subjects aged 13-84 years. It was found that in calcified tissues of teeth, the increase in concentration of Pb that occurs with age is a statistically significant process (p = 0.02, the ANOVA Kruskal-Wallis test). It was determined that the annual increase in concentration of Pb in tissues of teeth is approx. 0.1 μg/g. Moreover, a different course of changes in Pb concentration in tissues of teeth in people born in different years was observed. The level of Pb concentration in teeth of the oldest subjects (>60 years) decreased for those born in the 1930s compared to those in the 1950s. Teeth from younger persons (<60 years) were characterized by an increasing level of Pb concentration. The analysis of changes of Pb indicates that for low exposure, a relatively greater accumulation of Pb concentration in calcified tissues of teeth can occur.

  1. Morphological age-dependent development of the human carotid bifurcation.

    PubMed

    Seong, Jaehoon; Lieber, Baruch B; Wakhloo, Ajay K

    2005-03-01

    The unique morphology of the adult human carotid bifurcation and its sinus has been investigated extensively, but its long-term, age-dependent development has not. It is important fundamentally and clinically to understand the hemodynamics and developmental forces that play a role in remodeling of the carotid bifurcation and maturation of the sinus in association with brain maturation. This understanding can lead to better prognostication and therapy of carotid disease. We analyzed the change of sinus morphology and the angle of the carotid bifurcation in four postnatal developmental stages (Group I: 0-2 years, Group II: 3-9 years, Group III: 10-19 years, and Group IV: 20-36 years, respectively) using multiprojection digital subtraction angiograms and image post-processing techniques. The most significant findings are the substantial growth of the internal carotid artery (ICA) with age and the development of a carotid sinus at the root of the ICA during late adolescence. The bifurcation angle remains virtually unchanged from infancy to adulthood. However, the angle split between the ICA and external carotid artery (ECA) relative to the common carotid artery (CCA) undergoes significant changes. Initially, the ICA appears to emanate as a side branch. Later in life, to reduce hydraulic resistance in response to increased flow demand by the brain, the bifurcation is remodeled to a construct in which both daughter vessels are a skewed continuation of the parent artery. This study provides a new analysis method to examine the development of the human carotid bifurcation over the developmental years, despite the small and sparse database. A larger database will enable in the future a more extensive analysis such as gender or racial differences.

  2. FOUR-YEAR INCIDENCE AND PROGRESSION OF AGE-RELATED MACULAR DEGENERATION: THE LOS ANGELES LATINO EYE STUDY

    PubMed Central

    Varma, Rohit; Foong, Athena W.P.; Lai, Mei-Ying; Choudhury, Farzana; Klein, Ronald; Azen, Stanley P.

    2011-01-01

    Purpose To estimate 4-year incidence and progression of early and advanced age-related macular degeneration (AMD). Design Population-based cohort study. Methods A comprehensive ophthalmologic examination including stereoscopic fundus photography was performed on adult Latinos at baseline and follow-up. Photographs were graded using a modified Wisconsin Age-Related Maculopathy Grading System. For estimations of incidence and progression of AMD, the Age Related Eye Disease Study Scale was used. Main outcome measures are incidence and progression of early AMD (drusen type, drusen size, and retinal pigmentary abnormalities) and advanced AMD (exudative AMD and geographic atrophy). Results 4,658/6100 (76%) completed the follow-up examination. The 4-year incidence of early AMD was 7.5% (95%CI:6.6,8.4) and advanced AMD was 0.2% (95%CI:0.1,0.4). Progression of any AMD occurred in 9.3% (95%CI:8.4,10.3) of at-risk participants. Incidence and progression increased with age. Incidence of early AMD in the second eye (10.8%) was higher than incidence in the first eye (6.9%). Baseline presence of soft indistinct large drusen≥250μm in diameter was more likely to predict the 4-year incidence of pigmentary abnormalities, geographic atrophy, and exudative AMD than smaller or hard or soft distinct drusen. Conclusions Age-specific incidence and progression of AMD in Latinos are lower than in non-Hispanic whites. While incident early AMD is more often unilateral, the risk of its development in the second is higher than in the first eye. Older persons and those with soft indistinct large drusen had a higher risk of developing advanced AMD compared to those who were younger and did not have soft indistinct large drusen. PMID:20399926

  3. [Multiplex mapping of human cDNAs]. Technical progress report

    SciTech Connect

    Nierman, W.C.

    1991-12-31

    J. Craig Venter, National Institute of Neurological Disorders and Stroke, has begun to identify genes expressed in the human brain by partially sequences cDNA clones. We are collaborating with the Venter group and using their sequence data to develop methods for rapid localization of newly identified cDNAs to human chromosomes. We are applying the ABI automated DNA sequencer to the analysis of fluorescently-tagged PCR products for assigning sequences to individual human chromosomes. The steps in our mapping protocol are (1) to design PCR primers from the Venter laboratory-generated sequence data, (2) to test the primers for specific amplification from human genomic DNA, (3) to use the primers for PCR amplification from a somatic cell hybrid cell mapping panel, (4) to determine the presence or absence of the specific amplification products from each cell line DNA by electrophoretic analysis using the ABI sequencer, and (5) to analyze the pattern of amplification results from the hybrid panel to identify the chromosomal origin of the cDNA sequence. We have demonstrated the principle by mapping 12 sequences or ``Expressed Sequence Tags`` (ESTs), providing primer sequence data for subsequent subchromosomal localizations. We will now concentrate on developing methodology to allow multiplexing the amplification reactions and analysis of the reaction products, to achieve a high throughput with a minimum allocation of resources. This project will generate a data set from which to evaluate strategies to identify functional primer sequences from cDNA sequence data.

  4. [Developing a physical map of human chromosome 22]. Progress report

    SciTech Connect

    Simon, M.I.

    1991-12-31

    We have developed bacterial F-factor based systems for cloning large fragments of human DNA in E. coli. In addition to large size, these systems are capable of maintaining human DNA with a high degree of stability. The cosmid size clones are called Fosmids and the clones containing larger inserts (100--200 kb) are called bacterial artificial chromosomes (BACs). The ultimate test of the effectiveness of cloning and mapping technology is the degree to which it can be efficiently applied to solve complex mapping problems. We, therefore, plan to use the large fragment cloning procedure as well as a variety of other approaches to generate a complete map of overlapping clones corresponding to human chromosome 22. We have thus far prepared two human chromosome 22 specific Fosmid libraries and we are in the process of constructing a chromosome 22 specific BAC library composed of fragments larger than 100 kb. We will further optimize the technology so that libraries of fragments larger than 200 kb can be readily prepared.

  5. INCREASING SAVING BEHAVIOR THROUGH AGE-PROGRESSED RENDERINGS OF THE FUTURE SELF

    PubMed Central

    HERSHFIELD, HAL E.; GOLDSTEIN, DANIEL G.; SHARPE, WILLIAM F.; FOX, JESSE; YEYKELIS, LEO; CARSTENSEN, LAURA L.; BAILENSON, JEREMY N.

    2014-01-01

    Many people fail to save what they need to for retirement (Munnell, Webb, and Golub-Sass 2009). Research on excessive discounting of the future suggests that removing the lure of immediate rewards by pre-committing to decisions, or elaborating the value of future rewards can both make decisions more future-oriented. In this article, we explore a third and complementary route, one that deals not with present and future rewards, but with present and future selves. In line with thinkers who have suggested that people may fail, through a lack of belief or imagination, to identify with their future selves (Parfit 1971; Schelling 1984), we propose that allowing people to interact with age-progressed renderings of themselves will cause them to allocate more resources toward the future. In four studies, participants interacted with realistic computer renderings of their future selves using immersive virtual reality hardware and interactive decision aids. In all cases, those who interacted with virtual future selves exhibited an increased tendency to accept later monetary rewards over immediate ones. PMID:24634544

  6. INCREASING SAVING BEHAVIOR THROUGH AGE-PROGRESSED RENDERINGS OF THE FUTURE SELF.

    PubMed

    Hershfield, Hal E; Goldstein, Daniel G; Sharpe, William F; Fox, Jesse; Yeykelis, Leo; Carstensen, Laura L; Bailenson, Jeremy N

    2011-11-01

    Many people fail to save what they need to for retirement (Munnell, Webb, and Golub-Sass 2009). Research on excessive discounting of the future suggests that removing the lure of immediate rewards by pre-committing to decisions, or elaborating the value of future rewards can both make decisions more future-oriented. In this article, we explore a third and complementary route, one that deals not with present and future rewards, but with present and future selves. In line with thinkers who have suggested that people may fail, through a lack of belief or imagination, to identify with their future selves (Parfit 1971; Schelling 1984), we propose that allowing people to interact with age-progressed renderings of themselves will cause them to allocate more resources toward the future. In four studies, participants interacted with realistic computer renderings of their future selves using immersive virtual reality hardware and interactive decision aids. In all cases, those who interacted with virtual future selves exhibited an increased tendency to accept later monetary rewards over immediate ones.

  7. The Association of Statin Use with Age-Related Macular Degeneration Progression The Age-Related Eye Disease Study 2 Report Number 9

    PubMed Central

    Al-Holou, Shaza N.; Tucker, William R.; Agrón, Elvira; Clemons, Traci E.; Cukras, Catherine; Ferris, Frederick L.; Chew, Emily Y.

    2015-01-01

    Objective/purpose To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Design Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Subjects Age-Related Eye Disease Study 2 participants, aged 50 to 85 years. Methods Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke, all known to be associated with statin use, were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses were also performed adjusting for the competing risk of death. Main Outcome Measures Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Results Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratios [HR] of 1.08, 95% confidence intervals [CI] of 0.83–1.41, P=0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant with HR: 0.81, 95% CI: 0.55–1.20, P=0.29. Further subgroup analyses of persons with or without late AMD at baseline to the various components of late AMD (neovascular, central geographic atrophy, or any geographic atrophy) also showed no statistically significant association of statin use with progression to AMD. Conclusions Statin use was not statistically significantly associated with the

  8. Human Factors in Aviation Maintenance. Phase 2. Progress Report

    DTIC Science & Technology

    1993-04-01

    Industrial Engineering at the University of Buffalo. BioTechnology , Inc. prepared Chapter Six and worked with Galaxy Scientific to conduct the Human...shooting. Computers in Industr ’, pp. 187-202. Miller, F. D., Rowland, J. R., & Siegfried, E. M. (1986, January). ACE: An expert system for preventive...knowledge based expert system for maintenance trouble shooting. Compilers in Industr ’, pp. 187-202. Describes an expert system for diagnosis of the

  9. [Progress in Association between Genetic Correlation and Human Violent Behavior].

    PubMed

    Li, Hui; Li, Lei; Xu, Hong-mei; Zhao, Zi-qin; Liu, Wen-bin; Zhou, Huai-gu

    2015-10-01

    Human violent behavior is a complex behavior which is influenced by genetic and environmental factors. There is a trend in investigating the mechanism of violent behavior by using the genetic methods. This article reviews several candidate genes and advances in epigenetics which are associated with violent behavior. The prospects and significance of violent behavior research from the view of gene polymorphism and epigenetics are also discussed.

  10. Human Rights and Military Conduct: A Progress Report

    DTIC Science & Technology

    2000-01-01

    dilemma involves threats such as drug trafficking, organized crime, and terrorism . In most mature democracies responsibility for dealing with such threats...promoting reform to bolster civilian control and respect for human rights. That dilemma was underscored when Peruvian President Alberto Fujimori re...better guarantees could be assured. Asked whether he feared sanctions and a possible cutoff of aid from the United States, Fujimori replied, “What

  11. Passive biaxial mechanical response of aged human iliac arteries.

    PubMed

    Schulze-Bauer, Christian A J; Mörth, Christian; Holzapfel, Gerhard A

    2003-06-01

    Inflation and extension tests of arteries are essential for the understanding of arterial wall mechanics. Data for such tests of human arteries are rare. At autopsy we harvested 10 non-diseased external iliac arteries of aged subjects (52-87 yrs). Structural homogeneity was ensured by means of ultrasound imaging, and anamneses of patients were recorded. We measured the axial in situ stretches, load-free geometries and opening angles. Passive biaxial mechanical responses of preconditioned cylindrical specimens were studied in 37 degrees C calcium-free Tyrode solution under quasistatic loading conditions. Specimens were subjected to pressure cycles varying from 0 to 33.3 kPa (250 mmHg) at nine fixed axial loads, varying from 0 to 9.90N. For the description of the load-deformation behavior we employed five "two-dimensional" orthotropic strain-energy functions frequently used in arterial wall mechanics. The associated constitutive models were compared in regard to their ability of representing the experimental data. Histology showed that the arteries were of the muscular type. In contrast to animal arteries they exhibited intimal layers of considerable thickness. The average ratio of wall thickness to outer diameter was 7.7, which is much less than observed for common animal arteries. We found a clear correlation between age and the axial in situ stretch lambda is (r = -0.72, P = 0.03), and between age and distensibility of specimens, i.e. aged specimens are less distensible. Axial in situ stretches were clearly smaller (1.07 +/- 0.09, mean +/- SD) than in animal arteries. For one specimen lambda is was even smaller than 1.0, i.e. the vessel elongated axially upon excision. The nonlinear and anisotropic load-deformation behavior showed small hystereses. For the majority of specimens we observed axial stretches smaller than 1.3 and circumferential stretches smaller than 1.1 for the investigated loading range. Data from in situ inflation tests showed a significant

  12. [Progress in the knowledge of the intestinal human microbiota].

    PubMed

    Robles-Alonso, Virginia; Guarner, Francisco

    2013-01-01

    New sequencing technologies together with the development of bio-informatics allow a description of the full spectrum of the microbial communities that inhabit the human intestinal tract, as well as their functional contributions to host health. Most community members belong to the domain Bacteria, but Archaea, Eukaryotes (yeasts and protists), and Viruses are also present. Only 7 to 9 of the 55 known divisions or phyla of the domain Bacteria are detected in faecal or mucosal samples from the human gut. Most taxa belong to just two divisions: Bacteroidetes and Firmicutes, and the other divisions that have been consistently found are Proteobacteria, Actinobacteria, Fusobacteria, and Verrucomicrobia. Bacteroides, Faecalibacterium and Bifidobacterium are the most abundant genera but their relative proportion is highly variable across individuals. Full metagenomic analysis has identified more than 5 million non-redundant microbial genes encoding up to 20,000 biological functions related with life in the intestinal habitat. The overall structure of predominant genera in the human gut can be assigned into three robust clusters, which are known as "enterotypes". Each of the three enterotypes is identifiable by the levels of one of three genera: Bacteroides (enterotype 1), Prevotella (enterotype 2) and Ruminococcus (enterotype 3). This suggests that microbiota variations across individuals are stratified, not continuous. Next steps include the identification of changes that may play a role in certain disease states. A better knowledge of the contributions of microbial symbionts to host health will help in the design of interventions to improve symbiosis and combat disease.

  13. Arsenic and human health: epidemiologic progress and public health implications.

    PubMed

    Argos, Maria; Ahsan, Habibul; Graziano, Joseph H

    2012-09-10

    Elevated concentrations of arsenic in groundwater pose a public health threat to millions of people worldwide, including severely affected populations in South and Southeast Asia. Although arsenic is an established human carcinogen and has been associated with a multitude of health outcomes in epidemiologic studies, a mode of action has yet to be determined for some aspects of arsenic toxicity. Herein, we emphasize the role of recent genetic and molecular epidemiologic investigations of arsenic toxicity. Additionally, we discuss considerations for the public health impacts of arsenic exposure through drinking water with respect to primary and secondary prevention efforts.

  14. Similar slow down in running speed progression in species under human pressure.

    PubMed

    Desgorces, F-D; Berthelot, G; Charmantier, A; Tafflet, M; Schaal, K; Jarne, P; Toussaint, J-F

    2012-09-01

    Running speed in animals depends on both genetic and environmental conditions. Maximal speeds were here analysed in horses, dogs and humans using data sets on the 10 best performers covering more than a century of races. This includes a variety of distances in humans (200-1500 m). Speed has been progressing fast in the three species, and this has been followed by a plateau. Based on a Gompertz model, the current best performances reach 97.4% of maximal velocity in greyhounds to 100.3 in humans. Further analysis based on a subset of individuals and using an 'animal model' shows that running speed is heritable in horses (h(2) = 0.438, P = 0.01) and almost so in dogs (h(2) = 0.183, P = 0.08), suggesting the involvement of genetic factors. Speed progression in humans is more likely due to an enlarged population of runners, associated with improved training practices. The analysis of a data subset (40 last years in 800 and 1500 m) further showed that East Africans have strikingly improved their speed, now reaching the upper part of the human distribution, whereas that of Nordic runners stagnated in the 800 m and even declined in the 1500 m. Although speed progression in dogs and horses on one side and humans on the other has not been affected by the same genetic/environmental balance of forces, it is likely that further progress will be extremely limited.

  15. Effects of Caloric Restriction on Cardiovascular Aging in Non-human Primates and Humans

    PubMed Central

    Cruzen, Christina; Colman, Ricki J.

    2009-01-01

    Synopsis Approximately one in three Americans has some form of cardiovascular disease (CVD), accounting for one of every 2.8 deaths in the United States in 2004. Two of the major risk factors for CVD are advancing age and obesity. An intervention able to positively impact both aging and obesity, such as caloric restriction (CR), may prove extremely useful in the fight against CVD. CR is the only environmental or lifestyle intervention that has repeatedly been shown to increase maximum life span and to retard aging in laboratory rodents. In this article, we review evidence that CR in nonhuman primates and humans has a positive effect on risk factors for CVD. PMID:19944270

  16. Attenuated noradrenergic sensitivity during local cooling in aged human skin

    PubMed Central

    Thompson, Caitlin S; Holowatz, Lacy A; Kenney, W. Larry

    2005-01-01

    Reflex-mediated cutaneous vasoconstriction (VC) is impaired in older humans; however, it is unclear whether this blunted VC also occurs during local cooling, which mediates VC through different mechanisms. We tested the hypothesis that the sensitization of cutaneous vessels to noradrenaline (NA) during direct skin cooling seen in young skin is blunted in aged skin. In 11 young (18–30 years) and 11 older (62–76 years) men and women, skin blood flow was monitored at two forearm sites with laser Doppler (LD) flowmetry while local skin temperature was cooled and clamped at 24°C. Cutaneous vascular conductance (CVC; LD flux/mean arterial pressure) was expressed as percentage change from baseline (%ΔCVCbase). At one site, five doses of NA (10−10–10−2m) were sequentially infused via intradermal microdialysis during cooling while the other 24°C site served as control (Ringer solution + cooling). At control sites, VC due to cooling alone was similar in young versus older (−54 ± 5 versus −56 ± 3%ΔCVCbase, P= 0.46). In young, NA infusions induced additional dose-dependent VC (10−8, 10−6, 10−4 and 10−2m: −70 ± 2, −72 ± 3, −78 ± 3 and −79 ± 4%ΔCVCbase; P < 0.05 versus control). In older subjects, further VC did not occur until the highest infused dose of NA (10−2m: −70 ± 5%ΔCVCbase; P < 0.05 versus control). When cutaneous arterioles are sensitized to NA by direct cooling, young skin exhibits the capacity to further constrict to NA in a dose-dependent manner. However, older skin does not display enhanced VC capacity until treated with saturating doses of NA, possibly due to age-associated decrements in Ca2+ availability or α2C-adrenoceptor function. PMID:15705648

  17. Inverse correlation of genetic risk score with age at onset in bout-onset and progressive-onset multiple sclerosis.

    PubMed

    Sorosina, Melissa; Esposito, Federica; Guaschino, Clara; Clarelli, Ferdinando; Barizzone, Nadia; Osiceanu, Ana Maria; Brambilla, Paola; Mascia, Elisabetta; Cavalla, Paola; Gallo, Paolo; Martinelli, Vittorio; Leone, Maurizio; Comi, Giancarlo; D'Alfonso, Sandra; Martinelli Boneschi, Filippo

    2015-10-01

    We correlated the weighted genetic risk score measured using 107 established susceptibility variants for multiple sclerosis (MS) with the age at onset in bout-onset (BOMS, n=906) and progressive-onset MS Italian patients (PrMS) (n=544). We observed an opposite relationship in the two disease courses: a higher weighted genetic risk score was associated with an earlier age at onset in BOMS (rho= -0.1; p=5 × 10(-3)) and a later age at onset in PrMS cases (rho=0.07; p=0.15) (p of difference of regression=1.4 × 10(-2)). These findings suggest that established MS risk variants anticipate the onset of the inflammatory phase, while they have no impact on, or even delay, the onset of the progressive phase.

  18. Human Herpesviruses as Copathogens of HIV Infection, Their Role in HIV Transmission, and Disease Progression

    PubMed Central

    Munawwar, Arshi; Singh, Sarman

    2016-01-01

    Of eight human herpesviruses (HHVs), often, only herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) find mention in medical literature as both of these viruses are commonly associated with genital lesions and oral ulcers, commonly known as cold sores. However, role of human herpesviruses as copathogens and in aggravation and in the transmission of other human diseases, especially the Acquired immunodeficiency syndrome (HIV/AIDS) has only very recently been recognized. Therefore, screening and treating subclinical HHV infections may offer slowing of HIV infection, disease progression, and its transmission. Beside HSV-1 and HSV-2, HHV-3 a causative agent of herpes zoster remained one of the first manifestations of HIV disease before the era of highly active antiretroviral therapy (HAART). HHV-5 also known as human Cytomegalovirus infection remains a significant risk factor for HIV-associated mortality and morbidity even in HAART era. It is proposed that Cytomegalovirus viremia could be a better predictor of HIV disease progression than CD4+ T-lymphocyte count. The role of HHV-4 or Epstein–Burr virus and HHV-6, HHV-7, and HHV-8 is still being investigated in HIV disease progression. This review provides insight into the current understanding about these 8 HHVs, their co-pathogenesis, and role in HIV/AIDS disease progression. The review also covers recent literature in favor and against administering anti-HHV treatment along with HAART for slower AIDS progression and interrupted sexual transmission. PMID:27013807

  19. Self Antigen Prognostic for Human Immunodeficiency Virus Disease Progression

    PubMed Central

    Bristow, Cynthia L.; Patel, Hirenkumar; Arnold, Roland R.

    2001-01-01

    We have recently found that an extracellular protein, α1 proteinase inhibitor (α1PI; α1 antitrypsin), is required for in vitro human immunodeficiency virus (HIV) infectivity outcome. We show here in a study of HIV-seropositive patients that decreased viral load is significantly correlated with decreased circulating α1PI. In the asymptomatic category of HIV disease, 100% of patients manifest deficient levels of active α1PI, a condition known to lead to degenerative lung diseases and a dramatically reduced life span. Further, HIV-associated α1PI deficiency is correlated with circulating anti-α1PI immunoglobulin G. These results suggest that preventing HIV-associated α1PI deficiency may provide a strategic target for preventing HIV-associated pathophysiology. PMID:11527807

  20. Progress in stem cell therapy for major human neurological disorders.

    PubMed

    Martínez-Morales, P L; Revilla, A; Ocaña, I; González, C; Sainz, P; McGuire, D; Liste, I

    2013-10-01

    Human neurological disorders such as Alzheimer's disease (AD), Parkinson's disease, stroke or spinal cord injury are caused by the loss of neurons and glial cells in the brain or spinal cord in the Central Nervous System (CNS). Stem cell technology has become an attractive option to investigate and treat these diseases. Several types of neurons and glial cells have successfully been generated from stem cells, which in some cases, have ameliorated some dysfunctions both in animal models of neurological disorders and in patients at clinical level. Stem cell-based therapies can be beneficial by acting through several mechanisms such as cell replacement, modulation of inflammation and trophic actions. Here we review recent and current remarkable clinical studies involving stem cell-based therapy for AD and stroke and provide an overview of the different types of stem cells available nowadays, their main properties and how they are developing as a possible therapy for neurological disorders.

  1. Progress in the human geography of the Maghreb.

    PubMed

    Sutton, K; Lawless, R I

    1987-03-01

    Sutton and Lawless review a selection of the prolific literature on the Maghreb's human geography published from the late 1970s onward. The pedigree of the discipline in Maghreb was established by several notable geographers who lived, researched, and wrote there. Augustin Bernard's writings on rural settlement, his atlas, and study of Algeria are still cited. Jean Despois's regional study with Raynal and his work on Tunisia, together with the detailed rural research of Jean Poncet, provides a particularly rich coverage for that country. Jean Dresch's early work on Morocco exemplified an early critique of the contemporaneous uncritical colonial human geography. The Sahara's fascination also inspired pioneering studies by Robert Capot-Rey. The work of these notables and others provided a solid background of geographical literature on the Maghreb to be supplemented, criticized, and challenged by more recent researchers, sometimes pupils of the above individuals, and increasingly North African by birth. The tradition of general texts on the Maghreb has continued, though increasingly with systematic approaches replacing regional appraisals. The geography of the decolonization of the Maghreb by Isnard has been replaced by a study summarizing recent collaborative work by a team of French geographers. The Saharan extensions of the Maghreb states have often been linked in general works, sometimes being juxtaposed against the Maghreb as in the essays offered to Jean Despois. Lawless and Findlay's collaborative study juxtaposes geographical studies of each country's economic development with political scientists' evaluations of their sociopolitical development. This review limits itself largely to geographers and geographical journals, only occasionally including significant works from other subject areas, and to 1977-1978 publications, with a few notable exceptions. The spatial juxtaposition of contrasting approaches to economic development, liberal market economy

  2. Individual and Societal Wisdom: Explaining the Paradox of Human Aging and High Well-Being.

    PubMed

    Jeste, Dilip V; Oswald, Andrew J

    2014-03-26

    Objective: Although human aging is characterized by loss of fertility and progressive decline in physical abilities, later life is associated with better psychological health and well-being. Furthermore, there has been an unprecedented increase in average lifespan over the past century without corresponding extensions of fertile and healthy age spans. We propose a possible explanation for these paradoxical phenomena. Method: We reviewed the relevant literature on aging, well-being, and wisdom. Results: An increase in specific components of individual wisdom in later life may make up for the loss of fertility as well as declining physical health. However, current data on the relationship between aging and individual wisdom are not consistent and do not explain increased longevity in the general population during the past century. We propose that greater societal wisdom (including compassion) may account for the notable increase in average lifespan over the last century. Data in older adults with serious mental illnesses are limited, but suggest that many of them too experience improved psychosocial functioning, although their longevity has not yet increased, suggesting persistent stigma against mental illness and inadequate societal compassion. Conclusions: The proposed construct of societal wisdom needs more investigation. Research should also focus on the reasons for discrepant findings related to age-associated changes in different components of individual wisdom. Studies of wisdom and well-being are warranted in older people with serious mental illnesses, along with campaigns to enhance societal compassion for these disenfranchised individuals. Finally, effective interventions to enhance wisdom need to be developed and tested.

  3. Cerebrovascular and corticomotor function during progressive passive hyperthermia in humans.

    PubMed

    Ross, Emma Z; Cotter, James D; Wilson, Luke; Fan, Jui-Lin; Lucas, Samuel J E; Ainslie, Philip N

    2012-03-01

    The present study examined the integrative effects of passive heating on cerebral perfusion and alterations in central motor drive. Eight participants underwent passive hyperthermia [0.5°C increments in core temperature (Tc) from normothermia (37 ± 0.3°C) to their limit of thermal tolerance (T-LIM; 39.0 ± 0.4°C)]. Blood flow velocity in the middle cerebral artery (CBFv) and respiratory responses were measured continuously. Arterial blood gases and blood pressure were obtained intermittently. At baseline and each Tc level, supramaximal femoral nerve stimulation and transcranial magnetic stimulation (TMS) were performed to assess neuromuscular and cortical function, respectively. At T-LIM, measures were (in a randomized order) also made during a period of breathing 5% CO(2) gas to restore eucapnia (+5% CO(2)). Mean heating time was 179 ± 51 min, with each 0.5°C increment in Tc taking 40 ± 10 min. CBFv was reduced by ∼20% below baseline from +0.5°C until T-LIM. Maximal voluntary contraction (MVC) of the knee extensors was decreased at T-LIM (-9 ± 10%; P < 0.05), and cortical voluntary activation (VA), assessed by TMS, was decreased at +1.5°C and T-LIM by 11 ± 8 and 22 ± 23%, respectively (P < 0.05). Corticospinal excitability (measured as the EMG response produced by TMS) was unaltered. Reductions in cortical VA were related to changes in ventilation (Ve; R(2) = 0.76; P < 0.05) and partial pressure of end-tidal CO(2) (Pet(CO(2)); R(2) = 0.63; P < 0.05) and to changes in CBFv (R(2) = 0.61; P = 0.067). Interestingly, although CBFv was not fully restored, MVC and cortical VA were restored towards baseline values during inhalation of 5% CO(2). These results indicate that descending voluntary drive becomes progressively impaired as Tc is increased, presumably due, in part, to reductions in CBFv and to hyperthermia-induced hyperventilation and subsequent hypocapnia.

  4. 4-hydroxynonenal in the pathogenesis and progression of human diseases

    PubMed Central

    Shoeb, Mohammad; Ansari, Naseem H; Srivastava, Satish K; Ramana, Kota V

    2014-01-01

    Metastable aldehydes produced by lipid peroxidation act as 'toxic second messengers' that extend the injurious potential of free radicals. 4-hydroxy 2-nonenal (HNE), a highly toxic and most abundant stable end product of lipid peroxidation, has been implicated in the tissue damage, dysfunction, injury associated with aging and other pathological states such as cancer, Alzheimer, diabetes, cardiovascular and inflammatory complications. Further, HNE has been considered as a oxidative stress marker and it act as a secondary signaling molecule to regulates a number of cell signaling pathways. Biological activity of HNE depends on its intracellular concentration, which can differentially modulate cell death, growth and differentiation. Therefore, the mechanisms responsible for maintaining the intracellular levels of HNE are most important, not only in the defense against oxidative stress but also in the pathophysiology of a number of disease processes. In this review, we discusse the significance of HNE in mediating various disease processes and how regulation of its metabolism could be therapeutically effective. PMID:23848536

  5. Progressive age-related changes in sleep and EEG profiles in the PLB1Triple mouse model of Alzheimer's disease.

    PubMed

    Jyoti, Amar; Plano, Andrea; Riedel, Gernot; Platt, Bettina

    2015-10-01

    Sleep disturbances are common in Alzheimer's disease (AD) and now assumed to contribute to disease onset and progression. Here, we investigated whether activity, sleep/wake pattern, and electroencephalogram (EEG) profiles are altered in the knock-in PLB1Triple mouse model from 5 to 21 months of age. PLB1Triple mice displayed a progressive increase in wakefulness and non-rapid eye movement sleep fragmentation from 9 months onward, whereas PLB1WT wild type controls showed such deterioration only at 21 months. Impaired habituation to spatial novelty was also detected in PLB1Triple mice. Hippocampal power spectra of transgenic mice revealed progressive, vigilance stage-, brain region-, and age-specific changes. Age had an impact on EEG spectra in both cohorts but led to accelerated genotype-dependent differences, ultimately affecting all bands at 21 months. Overall, although PLB1Triple animals display only subtle amyloid and tau pathologies, robust sleep-wake and EEG abnormalities emerged. We hypothesize that such endophenotypes are sensitive, noninvasive, and reliable biomarker to identify onset and progression of AD.

  6. Natural and sun-induced aging of human skin.

    PubMed

    Rittié, Laure; Fisher, Gary J

    2015-01-05

    With worldwide expansion of the aging population, research on age-related pathologies is receiving growing interest. In this review, we discuss current knowledge regarding the decline of skin structure and function induced by the passage of time (chronological aging) and chronic exposure to solar UV irradiation (photoaging). Nearly every aspect of skin biology is affected by aging. The self-renewing capability of the epidermis, which provides vital barrier function, is diminished with age. Vital thermoregulation function of eccrine sweat glands is also altered with age. The dermal collagenous extracellular matrix, which comprises the bulk of skin and confers strength and resiliency, undergoes gradual fragmentation, which deleteriously impacts skin mechanical properties and dermal cell functions. Aging also affects wound repair, pigmentation, innervation, immunity, vasculature, and subcutaneous fat homeostasis. Altogether, age-related alterations of skin lead to age-related skin fragility and diseases.

  7. Natural and Sun-Induced Aging of Human Skin

    PubMed Central

    Rittié, Laure; Fisher, Gary J.

    2015-01-01

    With worldwide expansion of the aging population, research on age-related pathologies is receiving growing interest. In this review, we discuss current knowledge regarding the decline of skin structure and function induced by the passage of time (chronological aging) and chronic exposure to solar UV irradiation (photoaging). Nearly every aspect of skin biology is affected by aging. The self-renewing capability of the epidermis, which provides vital barrier function, is diminished with age. Vital thermoregulation function of eccrine sweat glands is also altered with age. The dermal collagenous extracellular matrix, which comprises the bulk of skin and confers strength and resiliency, undergoes gradual fragmentation, which deleteriously impacts skin mechanical properties and dermal cell functions. Aging also affects wound repair, pigmentation, innervation, immunity, vasculature, and subcutaneous fat homeostasis. Altogether, age-related alterations of skin lead to age-related skin fragility and diseases. PMID:25561721

  8. Interrelationship of age and diet in Romania's oldest human burial.

    PubMed

    Bonsall, Clive; Boroneanţ, Adina; Soficaru, Andrei; McSweeney, Kathleen; Higham, Tom; Miriţoiu, Nicolae; Pickard, Catriona; Cook, Gordon

    2012-04-01

    In 1968, excavations in the Climente II cave in the Iron Gates gorge of the River Danube in southwest Romania unearthed the skeleton of an adult male. The burial was assumed to be of Late Pleistocene age because of the presence of Late Upper Palaeolithic (LUP) artefacts in the cave. However, there was no strong supporting stratigraphic evidence, and the body position is reminiscent of Early Neolithic burial practice in the region. Here, we report the results of radiocarbon and stable isotope analyses of the Climente II skeleton, which show that the skeleton dates to the Bølling-Allerød Interstadial ~14,500 cal BP. This is several millennia older than any previously dated human remains from the Iron Gates region and confirms its status as the oldest known burial from Romania. The stable isotope results indicate a diet with an emphasis on aquatic resources, contrary to the commonly held view that the LUP inhabitants of the Iron Gates subsisted mainly by hunting large land mammals.

  9. Interrelationship of age and diet in Romania's oldest human burial

    NASA Astrophysics Data System (ADS)

    Bonsall, Clive; Boroneanţ, Adina; Soficaru, Andrei; McSweeney, Kathleen; Higham, Tom; Miriţoiu, Nicolae; Pickard, Catriona; Cook, Gordon

    2012-04-01

    In 1968, excavations in the Climente II cave in the Iron Gates gorge of the River Danube in southwest Romania unearthed the skeleton of an adult male. The burial was assumed to be of Late Pleistocene age because of the presence of Late Upper Palaeolithic (LUP) artefacts in the cave. However, there was no strong supporting stratigraphic evidence, and the body position is reminiscent of Early Neolithic burial practice in the region. Here, we report the results of radiocarbon and stable isotope analyses of the Climente II skeleton, which show that the skeleton dates to the Bølling-Allerød Interstadial ~14,500 cal BP. This is several millennia older than any previously dated human remains from the Iron Gates region and confirms its status as the oldest known burial from Romania. The stable isotope results indicate a diet with an emphasis on aquatic resources, contrary to the commonly held view that the LUP inhabitants of the Iron Gates subsisted mainly by hunting large land mammals.

  10. Human face processing is tuned to sexual age preferences

    PubMed Central

    Ponseti, J.; Granert, O.; van Eimeren, T.; Jansen, O.; Wolff, S.; Beier, K.; Deuschl, G.; Bosinski, H.; Siebner, H.

    2014-01-01

    Human faces can motivate nurturing behaviour or sexual behaviour when adults see a child or an adult face, respectively. This suggests that face processing is tuned to detecting age cues of sexual maturity to stimulate the appropriate reproductive behaviour: either caretaking or mating. In paedophilia, sexual attraction is directed to sexually immature children. Therefore, we hypothesized that brain networks that normally are tuned to mature faces of the preferred gender show an abnormal tuning to sexual immature faces in paedophilia. Here, we use functional magnetic resonance imaging (fMRI) to test directly for the existence of a network which is tuned to face cues of sexual maturity. During fMRI, participants sexually attracted to either adults or children were exposed to various face images. In individuals attracted to adults, adult faces activated several brain regions significantly more than child faces. These brain regions comprised areas known to be implicated in face processing, and sexual processing, including occipital areas, the ventrolateral prefrontal cortex and, subcortically, the putamen and nucleus caudatus. The same regions were activated in paedophiles, but with a reversed preferential response pattern. PMID:24850896

  11. Faster Increases in Human Life Expectancy Could Lead to Slower Population Aging

    PubMed Central

    2015-01-01

    Counterintuitively, faster increases in human life expectancy could lead to slower population aging. The conventional view that faster increases in human life expectancy would lead to faster population aging is based on the assumption that people become old at a fixed chronological age. A preferable alternative is to base measures of aging on people’s time left to death, because this is more closely related to the characteristics that are associated with old age. Using this alternative interpretation, we show that faster increases in life expectancy would lead to slower population aging. Among other things, this finding affects the assessment of the speed at which countries will age. PMID:25876033

  12. Faster increases in human life expectancy could lead to slower population aging.

    PubMed

    Sanderson, Warren C; Scherbov, Sergei

    2015-01-01

    Counterintuitively, faster increases in human life expectancy could lead to slower population aging. The conventional view that faster increases in human life expectancy would lead to faster population aging is based on the assumption that people become old at a fixed chronological age. A preferable alternative is to base measures of aging on people's time left to death, because this is more closely related to the characteristics that are associated with old age. Using this alternative interpretation, we show that faster increases in life expectancy would lead to slower population aging. Among other things, this finding affects the assessment of the speed at which countries will age.

  13. Inhibition of inflammation by pentosan polysulfate impedes the development and progression of severe diabetic nephropathy in aging C57B6 mice.

    PubMed

    Wu, Jin; Guan, Tian-jun; Zheng, Shirong; Grosjean, Fabrizio; Liu, Weicheng; Xiong, Huabao; Gordon, Ronald; Vlassara, Helen; Striker, Gary E; Zheng, Feng

    2011-10-01

    Inflammation has a key role in diabetic nephropathy (DN) progression. Pentosan polysulfate (PPS) has been shown to decreases interstitial inflammation and glomerulosclerosis in 5/6 nephrectomized rats. Since PPS has an excellent long-term safety profile in interstitial cystitis treatment, and we recently found that old diabetic C57B6 mice develop DN characterized by extensive tubulointerstitial inflammatory lesions that mimics human DN, we examined the effect of PPS on old diabetic mice. We also examined the anti-inflammatory properties of PPS in renal cells in vitro. Diabetes was induced with streptozotocin in 18 months female (early aging) C57B6 mice. Mice were then randomized to receive oral PPS (25 mg/kg/day) or water for 4 months. The effect of PPS on NF-κB activation and on TNFα, high glucose or advanced glycation end products (AGEs) stimulated proinflammatory gene expression in renal cells was examined. We found that PPS treatment preserved renal function, significantly reduced albuminuria, and markedly decreased the severity of renal lesions, including tubulointerstitial inflammation. PPS also reduced upregulation of TNFα and proinflammatory genes in aging diabetic kidneys. Furthermore, PPS suppressed NF-κB, decreased the proinflammatory actions of TNFα, and decreased high glucose and AGEs stimulated MCP-1 production in vitro. Finally, PPS decreased TNFα-induced increase in albumin permeability in podocyte monolayers. In conclusion, PPS treatment largely prevents the development/progression of nephropathy in aging diabetic mice. As this may be mediated by suppression of TNFα, high glucose, and AGE-stimulated NF-κB activation and inflammation in vitro, the in vivo blockade of DN may be due to the anti-inflammatory properties of PPS.

  14. Tau pathology in aged cynomolgus monkeys is progressive supranuclear palsy/corticobasal degeneration- but not Alzheimer disease-like -Ultrastructural mapping of tau by EDX.

    PubMed

    Uchihara, Toshiki; Endo, Kentaro; Kondo, Hiromi; Okabayashi, Sachi; Shimozawa, Nobuhiro; Yasutomi, Yasuhiro; Adachi, Eijiro; Kimura, Nobuyuki

    2016-11-14

    Concomitant deposition of amyloid -beta protein (Aβ) and neuronal tau as neurofibrillary tangles in the human brain is a hallmark of Alzheimer disease (AD). Because these deposits increase during normal aging, it has been proposed that aging brains may also undergo AD-like changes. To investigate the neuropathological changes that occur in the aging primate brain, we examined 21 brains of cynomolgus monkeys (7-36 years old) for Aβ- and tau-positive lesions. We found, 1) extensive deposition of Aβ in brains of cynomolgus monkeys over 25 years of age, 2) selective deposition of 4-repeat tau as pretangles in neurons, and as coiled body-like structures in oligodendroglia-like cells and astrocytes, 3) preferential distribution of tau in the basal ganglia and neocortex rather than the hippocampus, and 4) age-associated increases in 30-34 kDa AT8- and RD4-positive tau fragments in sarkosyl-insoluble fractions. We further labeled tau-positive structures using diaminobezidine enhanced with nickel, and visualized nickel-labeled structures by energy-dispersive X-ray (EDX) analysis of ultrathin sections. This allowed us to distinguish between nickel-labeled tau and background electron-dense structures, and we found that tau localized to 20-25 nm straight filaments in oligodendroglia-like cells and neurons. Our results indicate that the cytopathology and distribution of tau deposits in aged cynomolgus brains resemble those of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) rather than AD. Thus, even in the presence of Aβ, age-associated deposition of tau in non-human primates likely does not occur through AD-associated mechanisms.

  15. The identification of gene expression profiles associated with progression of human diabetic neuropathy

    PubMed Central

    Hur, Junguk; Sullivan, Kelli A.; Pande, Manjusha; Hong, Yu; Sima, Anders A. F.; Jagadish, Hosagrahar V.; Kretzler, Matthias

    2011-01-01

    Diabetic neuropathy is a common complication of diabetes. While multiple pathways are implicated in the pathophysiology of diabetic neuropathy, there are no specific treatments and no means to predict diabetic neuropathy onset or progression. Here, we identify gene expression signatures related to diabetic neuropathy and develop computational classification models of diabetic neuropathy progression. Microarray experiments were performed on 50 samples of human sural nerves collected during a 52-week clinical trial. A series of bioinformatics analyses identified differentially expressed genes and their networks and biological pathways potentially responsible for the progression of diabetic neuropathy. We identified 532 differentially expressed genes between patient samples with progressing or non-progressing diabetic neuropathy, and found these were functionally enriched in pathways involving inflammatory responses and lipid metabolism. A literature-derived co-citation network of the differentially expressed genes revealed gene subnetworks centred on apolipoprotein E, jun, leptin, serpin peptidase inhibitor E type 1 and peroxisome proliferator-activated receptor gamma. The differentially expressed genes were used to classify a test set of patients with regard to diabetic neuropathy progression. Ridge regression models containing 14 differentially expressed genes correctly classified the progression status of 92% of patients (P < 0.001). To our knowledge, this is the first study to identify transcriptional changes associated with diabetic neuropathy progression in human sural nerve biopsies and describe their potential utility in classifying diabetic neuropathy. Our results identifying the unique gene signature of patients with progressive diabetic neuropathy will facilitate the development of new mechanism-based diagnostics and therapies. PMID:21926103

  16. Five-Year Progression of Refractive Errors and Incidence of Myopia in School-Aged Children in Western China

    PubMed Central

    Zhou, Wen-Jun; Zhang, Yong-Ye; Li, Hua; Wu, Yu-Fei; Xu, Ji; Lv, Sha; Li, Ge; Liu, Shi-Chun; Song, Sheng-Fang

    2016-01-01

    Background To determine the change in refractive error and the incidence of myopia among school-aged children in the Yongchuan District of Chongqing City, Western China. Methods A population-based cross-sectional survey was initially conducted in 2006 among 3070 children aged 6 to 15 years. A longitudinal follow-up study was then conducted 5 years later between November 2011 and March 2012. Refractive error was measured under cycloplegia with autorefraction. Age, sex, and baseline refractive error were evaluated as risk factors for progression of refractive error and incidence of myopia. Results Longitudinal data were available for 1858 children (60.5%). The cumulative mean change in refractive error was −2.21 (standard deviation [SD], 1.87) diopters (D) for the entire study population, with an annual progression of refraction in a myopic direction of −0.43 D. Myopic progression of refractive error was associated with younger age, female sex, and higher myopic or hyperopic refractive error at baseline. The cumulative incidence of myopia, defined as a spherical equivalent refractive error of −0.50 D or more, among initial emmetropes and hyperopes was 54.9% (95% confidence interval [CI], 45.2%–63.5%), with an annual incidence of 10.6% (95% CI, 8.7%–13.1%). Myopia was found more likely to happen in female and older children. Conclusions In Western China, both myopic progression and incidence of myopia were higher than those of children from most other locations in China and from the European Caucasian population. Compared with a previous study in China, there was a relative increase in annual myopia progression and annual myopia incidence, a finding which is consistent with the increasing trend on prevalence of myopia in China. PMID:26875599

  17. Stress and memory in humans: twelve years of progress?

    PubMed

    Wolf, Oliver T

    2009-10-13

    Stress leads to an enhanced activity of the hypothalamus-pituitary adrenal (HPA) axis resulting in an increased release of glucocorticoids from the adrenal cortex. These hormones influence target systems in the periphery as well as in the brain. The present review paper describes the impact of the human stress hormone cortisol on episodic long-term memory. Starting out with our early observation that stress as well as cortisol treatment impaired declarative memory, experiments by the author are described, which result in an enhanced understanding of how cortisol influences memory. The main conclusions are that stress or cortisol treatment temporarily blocks memory retrieval. The effect is stronger for emotional arousing material independent of its valence. In addition cortisol only influences memory when a certain amount of testing induced arousal occurs. A functional magnetic resonance imaging (fMRI) study suggests that the neuronal correlate of the cortisol induced retrieval blockade is a reduced activity of the hippocampus. In contrast to the effects on retrieval cortisol enhances memory consolidation. Again this effect is often stronger for emotionally arousing material and sometimes occurs at the cost of memory for neutral material. A fMRI study revealed that higher cortisol levels were associated with a stronger amygdala response to emotional stimuli. Thus stimulatory effects of cortisol on this structure might underlie the cortisol induced enhancement of emotional memory consolidation. The findings presented are in line with models derived from experiments in rodents and are of relevance for our understanding of stress associated psychiatric disorders.

  18. CCN1 contributes to skin connective tissue aging by inducing age-associated secretory phenotype in human skin dermal fibroblasts.

    PubMed

    Quan, Taihao; Qin, Zhaoping; Robichaud, Patrick; Voorhees, John J; Fisher, Gary J

    2011-08-01

    Dermal connective tissue collagen is the major structural protein in skin. Fibroblasts within the dermis are largely responsible for collagen production and turnover. We have previously reported that dermal fibroblasts, in aged human skin in vivo, express elevated levels of CCN1, and that CCN1 negatively regulates collagen homeostasis by suppressing collagen synthesis and increasing collagen degradation (Quan et al. Am J Pathol 169:482-90, 2006, J Invest Dermatol 130:1697-706, 2010). In further investigations of CCN1 actions, we find that CCN1 alters collagen homeostasis by promoting expression of specific secreted proteins, which include matrix metalloproteinases and proinflammatory cytokines. We also find that CCN1-induced secretory proteins are elevated in aged human skin in vivo. We propose that CCN1 induces an "Age-Associated Secretory Phenotype", in dermal fibroblasts, which mediates collagen reduction and fragmentation in aged human skin.

  19. Age and Environment Influences on Mouse Prion Disease Progression: Behavioral Changes and Morphometry and Stereology of Hippocampal Astrocytes

    PubMed Central

    Bento-Torres, J.; Sobral, L. L.; de Oliveira, R. B.; Anthony, D. C.; Vasconcelos, P. F. C.

    2017-01-01

    Because enriched environment (EE) and exercise increase and aging decreases immune response, we hypothesized that environmental enrichment and aging will, respectively, delay and increase prion disease progression. Mice dorsal striatum received bilateral stereotaxic intracerebral injections of normal or ME7 prion infected mouse brain homogenates. After behavior analysis, animals were euthanized and their brains processed for astrocyte GFAP immunolabeling. Our analysis related to the environmental influence are limited to young adult mice, whereas age influence refers to aged mice raised on standard cages. Burrowing activity began to reduce in ME7-SE two weeks before ME7-EE, while no changes were apparent in ME7 aged mice (ME7-A). Object placement recognition was impaired in ME7-SE, NBH-A, and ME7-A but normal in all other groups. Object identity recognition was impaired in ME7-A. Cluster analysis revealed two morphological families of astrocytes in NBH-SE animals, three in NBH-A and ME7-A, and four in NBH-EE, ME7-SE, and ME7-EE. As compared with control groups, astrocytes from DG and CA3 prion-diseased animals show significant numerical and morphological differences and environmental enrichment did not reverse these changes but induced different morphological changes in GFAP+ hippocampal astroglia. We suggest that environmental enrichment and aging delayed hippocampal-dependent behavioral and neuropathological signs of disease progression. PMID:28243355

  20. Age and Environment Influences on Mouse Prion Disease Progression: Behavioral Changes and Morphometry and Stereology of Hippocampal Astrocytes.

    PubMed

    Bento-Torres, J; Sobral, L L; Reis, R R; de Oliveira, R B; Anthony, D C; Vasconcelos, P F C; Picanço Diniz, Cristovam Wanderley

    2017-01-01

    Because enriched environment (EE) and exercise increase and aging decreases immune response, we hypothesized that environmental enrichment and aging will, respectively, delay and increase prion disease progression. Mice dorsal striatum received bilateral stereotaxic intracerebral injections of normal or ME7 prion infected mouse brain homogenates. After behavior analysis, animals were euthanized and their brains processed for astrocyte GFAP immunolabeling. Our analysis related to the environmental influence are limited to young adult mice, whereas age influence refers to aged mice raised on standard cages. Burrowing activity began to reduce in ME7-SE two weeks before ME7-EE, while no changes were apparent in ME7 aged mice (ME7-A). Object placement recognition was impaired in ME7-SE, NBH-A, and ME7-A but normal in all other groups. Object identity recognition was impaired in ME7-A. Cluster analysis revealed two morphological families of astrocytes in NBH-SE animals, three in NBH-A and ME7-A, and four in NBH-EE, ME7-SE, and ME7-EE. As compared with control groups, astrocytes from DG and CA3 prion-diseased animals show significant numerical and morphological differences and environmental enrichment did not reverse these changes but induced different morphological changes in GFAP+ hippocampal astroglia. We suggest that environmental enrichment and aging delayed hippocampal-dependent behavioral and neuropathological signs of disease progression.

  1. Calorie restriction: decelerating mTOR-driven aging from cells to organisms (including humans).

    PubMed

    Blagosklonny, Mikhail V

    2010-02-15

    Although it has been known since 1917 that calorie restriction (CR) decelerates aging, the topic remains highly controversial. What might be the reason? Here I discuss that the anti-aging effect of CR rules out accumulation of DNA damage and failure of maintenance as a cause of aging. Instead, it suggests that aging is driven in part by the nutrient-sensing TOR (target of rapamycin) network. CR deactivates the TOR pathway, thus slowing aging and delaying diseases of aging. Humans are not an exception and CR must increase both maximal and healthy lifespan in humans to the same degree as it does in other mammals. Unlike mice, however, humans benefit from medical care, which prolongs lifespan despite accelerated aging in non-restricted individuals. Therefore in humans the effect of CR may be somewhat blunted. Still how much does CR extend human lifespan? And could this extension be surpassed by gerosuppressants such as rapamycin?

  2. Nutritional interventions protect against age-related deficits in behavior: from animals to humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aged rats show impaired performance on motor and cognitive tasks. Similar changes in behavior occur in humans with age, and the development of methods to retard or reverse these age-related neuronal and behavioral deficits could increase healthy aging and decrease health care costs. In the present s...

  3. Proteome-wide analysis reveals an age-associated cellular phenotype of in situ aged human fibroblasts

    PubMed Central

    Waldera-Lupa, Daniel M.; Kalfalah, Faiza; Florea, Ana-Maria; Sass, Steffen; Kruse, Fabian; Rieder, Vera; Tigges, Julia; Fritsche, Ellen; Krutmann, Jean; Busch, Hauke; Boerries, Melanie; Meyer, Helmut E.; Boege, Fritz; Theis, Fabian

    2014-01-01

    We analyzed an ex vivo model of in situ aged human dermal fibroblasts, obtained from 15 adult healthy donors from three different age groups using an unbiased quantitative proteome-wide approach applying label-free mass spectrometry. Thereby, we identified 2409 proteins, including 43 proteins with an age-associated abundance change. Most of the differentially abundant proteins have not been described in the context of fibroblasts’ aging before, but the deduced biological processes confirmed known hallmarks of aging and led to a consistent picture of eight biological categories involved in fibroblast aging, namely proteostasis, cell cycle and proliferation, development and differentiation, cell death, cell organization and cytoskeleton, response to stress, cell communication and signal transduction, as well as RNA metabolism and translation. The exhaustive analysis of protein and mRNA data revealed that 77% of the age-associated proteins were not linked to expression changes of the corresponding transcripts. This is in line with an associated miRNA study and led us to the conclusion that most of the age-associated alterations detected at the proteome level are likely caused post-transcriptionally rather than by differential gene expression. In summary, our findings led to the characterization of novel proteins potentially associated with fibroblast aging and revealed that primary cultures of in situ aged fibroblasts are characterized by moderate age-related proteomic changes comprising the multifactorial process of aging. PMID:25411231

  4. The transcriptional landscape of age in human peripheral blood.

    PubMed

    Peters, Marjolein J; Joehanes, Roby; Pilling, Luke C; Schurmann, Claudia; Conneely, Karen N; Powell, Joseph; Reinmaa, Eva; Sutphin, George L; Zhernakova, Alexandra; Schramm, Katharina; Wilson, Yana A; Kobes, Sayuko; Tukiainen, Taru; Ramos, Yolande F; Göring, Harald H H; Fornage, Myriam; Liu, Yongmei; Gharib, Sina A; Stranger, Barbara E; De Jager, Philip L; Aviv, Abraham; Levy, Daniel; Murabito, Joanne M; Munson, Peter J; Huan, Tianxiao; Hofman, Albert; Uitterlinden, André G; Rivadeneira, Fernando; van Rooij, Jeroen; Stolk, Lisette; Broer, Linda; Verbiest, Michael M P J; Jhamai, Mila; Arp, Pascal; Metspalu, Andres; Tserel, Liina; Milani, Lili; Samani, Nilesh J; Peterson, Pärt; Kasela, Silva; Codd, Veryan; Peters, Annette; Ward-Caviness, Cavin K; Herder, Christian; Waldenberger, Melanie; Roden, Michael; Singmann, Paula; Zeilinger, Sonja; Illig, Thomas; Homuth, Georg; Grabe, Hans-Jörgen; Völzke, Henry; Steil, Leif; Kocher, Thomas; Murray, Anna; Melzer, David; Yaghootkar, Hanieh; Bandinelli, Stefania; Moses, Eric K; Kent, Jack W; Curran, Joanne E; Johnson, Matthew P; Williams-Blangero, Sarah; Westra, Harm-Jan; McRae, Allan F; Smith, Jennifer A; Kardia, Sharon L R; Hovatta, Iiris; Perola, Markus; Ripatti, Samuli; Salomaa, Veikko; Henders, Anjali K; Martin, Nicholas G; Smith, Alicia K; Mehta, Divya; Binder, Elisabeth B; Nylocks, K Maria; Kennedy, Elizabeth M; Klengel, Torsten; Ding, Jingzhong; Suchy-Dicey, Astrid M; Enquobahrie, Daniel A; Brody, Jennifer; Rotter, Jerome I; Chen, Yii-Der I; Houwing-Duistermaat, Jeanine; Kloppenburg, Margreet; Slagboom, P Eline; Helmer, Quinta; den Hollander, Wouter; Bean, Shannon; Raj, Towfique; Bakhshi, Noman; Wang, Qiao Ping; Oyston, Lisa J; Psaty, Bruce M; Tracy, Russell P; Montgomery, Grant W; Turner, Stephen T; Blangero, John; Meulenbelt, Ingrid; Ressler, Kerry J; Yang, Jian; Franke, Lude; Kettunen, Johannes; Visscher, Peter M; Neely, G Gregory; Korstanje, Ron; Hanson, Robert L; Prokisch, Holger; Ferrucci, Luigi; Esko, Tonu; Teumer, Alexander; van Meurs, Joyce B J; Johnson, Andrew D

    2015-10-22

    Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.

  5. The transcriptional landscape of age in human peripheral blood

    PubMed Central

    Peters, Marjolein J.; Joehanes, Roby; Pilling, Luke C.; Schurmann, Claudia; Conneely, Karen N.; Powell, Joseph; Reinmaa, Eva; Sutphin, George L.; Zhernakova, Alexandra; Schramm, Katharina; Wilson, Yana A.; Kobes, Sayuko; Tukiainen, Taru; Nalls, Michael A.; Hernandez, Dena G.; Cookson, Mark R.; Gibbs, Raphael J.; Hardy, John; Ramasamy, Adaikalavan; Zonderman, Alan B.; Dillman, Allissa; Traynor, Bryan; Smith, Colin; Longo, Dan L.; Trabzuni, Daniah; Troncoso, Juan; van der Brug, Marcel; Weale, Michael E.; O'Brien, Richard; Johnson, Robert; Walker, Robert; Zielke, Ronald H.; Arepalli, Sampath; Ryten, Mina; Singleton, Andrew B.; Ramos, Yolande F.; Göring, Harald H. H.; Fornage, Myriam; Liu, Yongmei; Gharib, Sina A.; Stranger, Barbara E.; De Jager, Philip L.; Aviv, Abraham; Levy, Daniel; Murabito, Joanne M.; Munson, Peter J.; Huan, Tianxiao; Hofman, Albert; Uitterlinden, André G.; Rivadeneira, Fernando; van Rooij, Jeroen; Stolk, Lisette; Broer, Linda; Verbiest, Michael M. P. J.; Jhamai, Mila; Arp, Pascal; Metspalu, Andres; Tserel, Liina; Milani, Lili; Samani, Nilesh J.; Peterson, Pärt; Kasela, Silva; Codd, Veryan; Peters, Annette; Ward-Caviness, Cavin K.; Herder, Christian; Waldenberger, Melanie; Roden, Michael; Singmann, Paula; Zeilinger, Sonja; Illig, Thomas; Homuth, Georg; Grabe, Hans-Jörgen; Völzke, Henry; Steil, Leif; Kocher, Thomas; Murray, Anna; Melzer, David; Yaghootkar, Hanieh; Bandinelli, Stefania; Moses, Eric K.; Kent, Jack W.; Curran, Joanne E.; Johnson, Matthew P.; Williams-Blangero, Sarah; Westra, Harm-Jan; McRae, Allan F.; Smith, Jennifer A.; Kardia, Sharon L. R.; Hovatta, Iiris; Perola, Markus; Ripatti, Samuli; Salomaa, Veikko; Henders, Anjali K.; Martin, Nicholas G.; Smith, Alicia K.; Mehta, Divya; Binder, Elisabeth B.; Nylocks, K Maria; Kennedy, Elizabeth M.; Klengel, Torsten; Ding, Jingzhong; Suchy-Dicey, Astrid M.; Enquobahrie, Daniel A.; Brody, Jennifer; Rotter, Jerome I.; Chen, Yii-Der I.; Houwing-Duistermaat, Jeanine; Kloppenburg, Margreet; Slagboom, P. Eline; Helmer, Quinta; den Hollander, Wouter; Bean, Shannon; Raj, Towfique; Bakhshi, Noman; Wang, Qiao Ping; Oyston, Lisa J.; Psaty, Bruce M.; Tracy, Russell P.; Montgomery, Grant W.; Turner, Stephen T.; Blangero, John; Meulenbelt, Ingrid; Ressler, Kerry J.; Yang, Jian; Franke, Lude; Kettunen, Johannes; Visscher, Peter M.; Neely, G. Gregory; Korstanje, Ron; Hanson, Robert L.; Prokisch, Holger; Ferrucci, Luigi; Esko, Tonu; Teumer, Alexander; van Meurs, Joyce B. J.; Johnson, Andrew D.

    2015-01-01

    Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the ‘transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts. PMID:26490707

  6. (Mis)Understanding Human Beings: Theory, Value, and Progress in Education Research

    ERIC Educational Resources Information Center

    Hostetler, Karl

    2010-01-01

    There is renewed interest in what can be called an "experimentist" approach to education research. The claim is that if researchers would focus on experiments and "evidence-based" policies and practices, irreversible progress in education can be achieved. This experimentist approach cannot provide the understanding of knowledge and human beings…

  7. Can HMG Co-A reductase inhibitors (“statins”) slow the progression of age-related macular degeneration? The Age-Related Maculopathy Statin Study (ARMSS)

    PubMed Central

    Guymer, Robyn H; Dimitrov, Peter N; Varsamidis, Mary; Lim, Lyndell L; Baird, Paul N; Vingrys, Algis J; Robman, Luba

    2008-01-01

    Age-related macular degeneration (AMD) is responsible for the majority of visual impairment in the Western world. The role of cholesterol-lowering medications, HMG Co-A reductase inhibitors or statins, in reducing the risk of AMD or of delaying its progression has not been fully investigated. A 3-year prospective randomized controlled trial of 40 mg simvastatin per day compared to placebo in subjects at high risk of AMD progression is described. This paper outlines the primary aims of the Age-Related Maculopathy Statin Study (ARMSS), and the methodology involved. Standardized clinical grading of macular photographs and comparison of serial macular digital photographs, using the International grading scheme, form the basis for assessment of primary study outcomes. In addition, macular function is assessed at each visit with detailed psychophysical measurements of rod and cone function. Information collected in this study will assist in the assessment of the potential value of HMG Co-A reductase inhibitors (statins) in reducing the risk of AMD progression. PMID:18982929

  8. New 40Ar/39Ar Ages for Savai'i Island Reinstate Samoa as a Hotspot Trail with a Linear Age Progression

    NASA Astrophysics Data System (ADS)

    Koppers, A. A.; Russell, J. A.; Staudigel, H.; Hart, S. R.

    2006-12-01

    The volcanic islands and seamounts of the Samoan Archipelago have long been considered problematic in terms of the hotspot hypothesis. Existing K/Ar and 40Ar/39Ar measurements on subaerial samples from the Samoan islands have consistently given ages that are too young by several Myrs, conflicting with the expected linear age progression model. Previous data from the volcanic series and cones on Savai'i Island gave a range of ages between 0.2 and 2.1 Ma. This is in contrast to an age of 5.2 Ma that a Pacific plate motion of 7.1 cm/yr would predict for the onset of the shield building stage on Savai'i (Workman et al. 2004). The oldest shield ages for the islands of Upolu (2.7 My) and Tutuila (1.6 My) young eastward, toward the volcanically active Vailulu'u seamount that marks the current location of the Samoan hotspot (Hart et al. 2000; Staudigel et al. 2006). However, these ages are younger than predicted by the plate-speed model with 4.4 My and 2.7 My, respectively. The omnipresence of only young post-erosional volcanism on Savai'i has lead to extensive discussions on the origin of Samoan volcanism, and is often used as an argument against a possible hotspot and mantle plume origin. We present new 40Ar/39Ar data on volcanic samples from the deep flanks and rifts of Savai'i and a group of Samoan seamounts that were dredged during the ALIA Expedition. Twelve ages from eight different dredge locations confirm the predicted 7.1 cm/yr age progression for the Samoan hotspot. Three different volcanic samples from dredge ALIA-115, on the deepest portion of the SW flank of Savai'i Island, give indistinguishable ages (2σ confidence level) ranging from 4.99 to 5.21 Ma. In addition, a sample from dredge ALIA-128, on the NE flank of Savai'i, gives an age of 4.74 Ma. These results clearly demonstrate that the onset of the shield-building stage on Savai'i occurred much earlier than the oldest volcanics (2.1 Ma) sampled subaerially on the island. Sr-Nd-Pb isotopes and trace

  9. PET Imaging of Tau Deposition in the Aging Human Brain

    PubMed Central

    Schonhaut, Daniel R.; O’Neil, James P.; Janabi, Mustafa; Ossenkoppele, Rik; Baker, Suzanne L.; Vogel, Jacob W.; Faria, Jamie; Schwimmer, Henry D.; Rabinovici, Gil D.; Jagust, William J.

    2016-01-01

    SUMMARY Tau pathology is a hallmark of Alzheimer’s disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent 18F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid, and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition. PMID:26938442

  10. The fractal based analysis of human face and DNA variations during aging.

    PubMed

    Namazi, Hamidreza; Akrami, Amin; Hussaini, Jamal; Silva, Osmar N; Wong, Albert; Kulish, Vladimir V

    2017-01-16

    Human DNA is the main unit that shapes human characteristics and features such as behavior. Thus, it is expected that changes in DNA (DNA mutation) influence human characteristics and features. Face is one of the human features which is unique and also dependent on his gen. In this paper, for the first time we analyze the variations of human DNA and face simultaneously. We do this job by analyzing the fractal dimension of DNA walk and face during human aging. The results of this study show the human DNA and face get more complex by aging. These complexities are mapped on fractal exponents of DNA walk and human face. The method discussed in this paper can be further developed in order to investigate the direct influence of DNA mutation on the face variations during aging, and accordingly making a model between human face fractality and the complexity of DNA walk.

  11. The National Institutes of Health Center for Human Immunology, Autoimmunity, and Inflammation: history and progress.

    PubMed

    Dickler, Howard B; McCoy, J Philip; Nussenblatt, Robert; Perl, Shira; Schwartzberg, Pamela A; Tsang, John S; Wang, Ena; Young, Neil S

    2013-05-01

    The Center for Human Immunology, Autoimmunity, and Inflammation (CHI) is an exciting initiative of the NIH intramural program begun in 2009. It is uniquely trans-NIH in support (multiple institutes) and leadership (senior scientists from several institutes who donate their time). Its goal is an in-depth assessment of the human immune system using high-throughput multiplex technologies for examination of immune cells and their products, the genome, gene expression, and epigenetic modulation obtained from individuals both before and after interventions, adding information from in-depth clinical phenotyping, and then applying advanced biostatistical and computer modeling methods for mining these diverse data. The aim is to develop a comprehensive picture of the human "immunome" in health and disease, elucidate common pathogenic pathways in various diseases, identify and validate biomarkers that predict disease progression and responses to new interventions, and identify potential targets for new therapeutic modalities. Challenges, opportunities, and progress are detailed.

  12. The Use of Microperimetry to Detect Functional Progression in Non-Neovascular Age-Related Macular Degeneration: A Systematic Review.

    PubMed

    Wong, Evan N; Chew, Avenell L; Morgan, William H; Patel, Praveen J; Chen, Fred K

    2017-01-01

    We reviewed the current literature on the ability of microperimetry to detect non-neovascular age-related macular degeneration (AMD) disease progression. The index test was retinal sensitivity measurement assessed by microperimetry and comparators were other functional measures (best-corrected and low-luminance visual acuities, and fixation stability) and structural parameters [retinal thickness, choroidal thickness, and area of geographic atrophy (GA) determined by color fundus photographs, short-wave or near-infrared fundus autofluorescence]. The reference standard was area of GA. The literature search was conducted in January 2016 and included MEDLINE, EMBASE, the Cochrane Library, Biosis, Science Citation Index, ProQuest Health and Medicine, CINAHL, and Highwire Press. We included 6 studies that enrolled 41 eyes with intermediate AMD (from a single study) and 80 eyes with GA secondary to AMD. Retinal sensitivity measured by microperimetry was the only functional measure that consistently detected progression in each cohort. Insufficient reported data precluded meta-analysis. Various microperimetry parameters were used to assess cohort-level change in retinal sensitivity, but the methods of analysis have yet to mature in complexity in comparison with established glaucoma field progression analysis. Microperimetry-assessed retinal sensitivity measurement may be more sensitive in detecting progression than other functional measures in non-neovascular AMD. However, the lack of standardized testing protocol and methods of progression analysis hindered comparison. Harmonization of testing protocol and development of more robust methods of analyzing raw microperimetric data will facilitate clinical implementation of this valuable retinal assessment tool.

  13. Gene expression profiles associated with aging and mortality in humans

    PubMed Central

    Kerber, Richard A; O’Brien, Elizabeth; Cawthon, Richard M

    2009-01-01

    We investigated the hypothesis that gene expression profiles in cultured cell lines from adults, aged 57–97 years, contain information about the biological age and potential longevity of the donors. We studied 104 unrelated grandparents from 31 Utah CEU (Centre d’Etude du Polymorphisme Humain – Utah) families, for whom lymphoblastoid cell lines were established in the 1980s. Combining publicly available gene expression data from these cell lines, and survival data from the Utah Population Database, we tested the relationship between expression of 2151 always-expressed genes, age, and survival of the donors. Approximately 16% of 2151 expression levels were associated with donor age: 10% decreased in expression with age, and 6% increased with age. Cell division cycle 42 (CDC42) and CORO1A exhibited strong associations both with age at draw and survival after draw (multiple comparisons-adjusted Monte Carlo P-value < 0.05). In general, gene expressions that increased with age were associated with increased mortality. Gene expressions that decreased with age were generally associated with reduced mortality. A multivariate estimate of biological age modeled from expression data was dominated by CDC42 expression, and was a significant predictor of survival after blood draw. A multivariate model of survival as a function of gene expression was dominated by CORO1A expression. This model accounted for approximately 23% of the variation in survival among the CEU grandparents. Some expression levels were negligibly associated with age in this cross-sectional dataset, but strongly associated with inter-individual differences in survival. These observations may lead to new insights regarding the genetic contribution to exceptional longevity. PMID:19245677

  14. Gene expression profiles associated with aging and mortality in humans.

    PubMed

    Kerber, Richard A; O'Brien, Elizabeth; Cawthon, Richard M

    2009-06-01

    We investigated the hypothesis that gene expression profiles in cultured cell lines from adults, aged 57-97 years, contain information about the biological age and potential longevity of the donors. We studied 104 unrelated grandparents from 31 Utah CEU (Centre d'Etude du Polymorphisme Humain - Utah) families, for whom lymphoblastoid cell lines were established in the 1980s. Combining publicly available gene expression data from these cell lines, and survival data from the Utah Population Database, we tested the relationship between expression of 2151 always-expressed genes, age, and survival of the donors. Approximately 16% of 2151 expression levels were associated with donor age: 10% decreased in expression with age, and 6% increased with age. Cell division cycle 42 (CDC42) and CORO1A exhibited strong associations both with age at draw and survival after draw (multiple comparisons-adjusted Monte Carlo P-value < 0.05). In general, gene expressions that increased with age were associated with increased mortality. Gene expressions that decreased with age were generally associated with reduced mortality. A multivariate estimate of biological age modeled from expression data was dominated by CDC42 expression, and was a significant predictor of survival after blood draw. A multivariate model of survival as a function of gene expression was dominated by CORO1A expression. This model accounted for approximately 23% of the variation in survival among the CEU grandparents. Some expression levels were negligibly associated with age in this cross-sectional dataset, but strongly associated with inter-individual differences in survival. These observations may lead to new insights regarding the genetic contribution to exceptional longevity.

  15. Role of microRNAs in the age-related changes in skeletal muscle and diet or exercise interventions to promote healthy aging in humans.

    PubMed

    McGregor, Robin A; Poppitt, Sally D; Cameron-Smith, David

    2014-09-01

    Progressive age-related changes in skeletal muscle mass and composition, underpin decreases in muscle function, which can inturn lead to impaired mobility and quality of life in older adults. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in skeletal muscle and are associated with aging. Accumulating evidence suggests that miRNAs play an important role in the age-related changes in skeletal muscle mass, composition and function. At the cellular level, miRNAs have been demonstrated to regulate muscle cell proliferation and differentiation. Furthermore, miRNAs are involved in the transitioning of muscle stem cells from a quiescent, to either an activated or senescence state. Evidence from animal and human studies has shown miRNAs are modulated in muscle atrophy and hypertrophy. In addition, miRNAs have been implicated in changes in muscle fiber composition, fat infiltration and insulin resistance. Both exercise and dietary interventions can combat age-related changes in muscle mass, composition and function, which may be mediated by miRNA modulation in skeletal muscle. Circulating miRNA species derived from myogenic cell populations represent potential biomarkers of aging muscle and the molecular responses to exercise or diet interventions, but larger validation studies are required. In future therapeutic approaches targeting miRNAs, either through exercise, diet or drugs may be able to slow down or prevent the age-related changes in skeletal muscle mass, composition, function, hence help maintain mobility and quality of life in old age.

  16. MALDI Imaging Mass Spectrometry Spatially Maps Age-Related Deamidation and Truncation of Human Lens Aquaporin-0

    PubMed Central

    Wenke, Jamie L.; Rose, Kristie L.; Spraggins, Jeffrey M.; Schey, Kevin L.

    2015-01-01

    Purpose To spatially map human lens Aquaporin-0 (AQP0) protein modifications, including lipidation, truncation, and deamidation, from birth through middle age using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS). Methods Human lens sections were water-washed to facilitate detection of membrane protein AQP0. We acquired MALDI images from eight human lenses ranging in age from 2 months to 63 years. In situ tryptic digestion was used to generate peptides of AQP0 and peptide images were acquired on a 15T Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Peptide extracts were analyzed by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and database searched to identify peptides observed in MALDI imaging experiments. Results Unmodified, truncated, and fatty acid–acylated forms of AQP0 were detected in protein imaging experiments. Full-length AQP0 was fatty acid acylated in the core and cortex of young (2- and 4-month) lenses. Acylated and unmodified AQP0 were C-terminally truncated in older lens cores. Deamidated tryptic peptides (+0.9847 Da) were mass resolved from unmodified peptides by FTICR MS. Peptide images revealed differential localization of un-, singly-, and doubly-deamidated AQP0 C-terminal peptide (239–263). Deamidation was present at 4 months and increases with age. Liquid chromatography–MS/MS results indicated N246 undergoes deamidation more rapidly than N259. Conclusions Results indicated AQP0 fatty acid acylation and deamidation occur during early development. Progressive age-related AQP0 processing, including deamidation and truncation, was mapped in human lenses as a function of age. The localization of these modified AQP0 forms suggests where AQP0 functions may change throughout lens development and aging. PMID:26574799

  17. Progressive squamous epithelial neoplasia in K14-human papillomavirus type 16 transgenic mice.

    PubMed Central

    Arbeit, J M; Münger, K; Howley, P M; Hanahan, D

    1994-01-01

    To model human papillomavirus-induced neoplastic progression, expression of the early region of human papillomavirus type 16 (HPV16) was targeted to the basal cells of the squamous epithelium in transgenic mice, using a human keratin 14 (K14) enhancer/promoter. Twenty-one transgenic founder mice were produced, and eight lines carrying either wild-type or mutant HPV16 early regions that did not express the E1 or E2 genes were established. As is characteristic of human cancers, the E6 and E7 genes remained intact in these mutants. The absence of E1 or E2 function did not influence the severity of the phenotype that eventually developed in the transgenic mice. Hyperplasia, papillomatosis, and dysplasia appeared at multiple epidermal and squamous mucosal sites, including ear and truncal skin, face, snout and eyelids, and anus. The ears were the most consistently affected site, with pathology being present in all lines with 100% penetrance. This phenotype also progressed through discernible stages. An initial mild hyperplasia was followed by hyperplasia, which further progressed to dysplasia and papillomatosis. During histopathological progression, there was an incremental increase in cellular DNA synthesis, determined by 5-bromo-2'-deoxyuridine incorporation, and a profound perturbation in keratinocyte terminal differentiation, as revealed by immunohistochemistry to K5, K14, and K10 and filaggrin. These K14-HPV16 transgenic mice present an opportunity to study the role of the HPV16 oncogenes in the neoplastic progression of squamous epithelium and provide a model with which to identify genetic and epigenetic factors necessary for carcinogenesis. Images PMID:7515971

  18. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Progress report, July 1992--August 1993

    SciTech Connect

    Rowley, J.D.

    1993-09-01

    Progress in identification of chromosomal transformations associated with leukemogenesis is described. In particular progress in DNA cloning of chromosomal break points in human cancer patients is described.

  19. Biodemography of old-age mortality in humans and rodents.

    PubMed

    Gavrilova, Natalia S; Gavrilov, Leonid A

    2015-01-01

    The growing number of persons living beyond age 80 underscores the need for accurate measurement of mortality at advanced ages and understanding the old-age mortality trajectories. It is believed that exponential growth of mortality with age (Gompertz law) is followed by a period of deceleration, with slower rates of mortality increase at older ages. This pattern of mortality deceleration is traditionally described by the logistic (Kannisto) model, which is considered as an alternative to the Gompertz model. Mortality deceleration was observed for many invertebrate species, but the evidence for mammals is controversial. We compared the performance (goodness-of-fit) of two competing models-the Gompertz model and the logistic (Kannisto) model using data for three mammalian species: 22 birth cohorts of U.S. men and women, eight cohorts of laboratory mice, and 10 cohorts of laboratory rats. For all three mammalian species, the Gompertz model fits mortality data significantly better than the "mortality deceleration" Kannisto model (according to the Akaike's information criterion as the goodness-of-fit measure). These results suggest that mortality deceleration at advanced ages is not a universal phenomenon, and survival of mammalian species follows the Gompertz law up to very old ages.

  20. Biodemography of Old-Age Mortality in Humans and Rodents

    PubMed Central

    Gavrilov, Leonid A.

    2015-01-01

    The growing number of persons living beyond age 80 underscores the need for accurate measurement of mortality at advanced ages and understanding the old-age mortality trajectories. It is believed that exponential growth of mortality with age (Gompertz law) is followed by a period of deceleration, with slower rates of mortality increase at older ages. This pattern of mortality deceleration is traditionally described by the logistic (Kannisto) model, which is considered as an alternative to the Gompertz model. Mortality deceleration was observed for many invertebrate species, but the evidence for mammals is controversial. We compared the performance (goodness-of-fit) of two competing models—the Gompertz model and the logistic (Kannisto) model using data for three mammalian species: 22 birth cohorts of U.S. men and women, eight cohorts of laboratory mice, and 10 cohorts of laboratory rats. For all three mammalian species, the Gompertz model fits mortality data significantly better than the “mortality deceleration” Kannisto model (according to the Akaike’s information criterion as the goodness-of-fit measure). These results suggest that mortality deceleration at advanced ages is not a universal phenomenon, and survival of mammalian species follows the Gompertz law up to very old ages. PMID:24534516

  1. Age-related telomere uncapping is associated with cellular senescence and inflammation independent of telomere shortening in human arteries.

    PubMed

    Morgan, Richard G; Ives, Stephen J; Lesniewski, Lisa A; Cawthon, Richard M; Andtbacka, Robert H I; Noyes, R Dirk; Richardson, Russell S; Donato, Anthony J

    2013-07-15

    Arterial telomere dysfunction may contribute to chronic arterial inflammation by inducing cellular senescence and subsequent senescence-associated inflammation. Although telomere shortening has been associated with arterial aging in humans, age-related telomere uncapping has not been described in non-cultured human tissues and may have substantial prognostic value. In skeletal muscle feed arteries from 104 younger, middle-aged, and older adults, we assessed the potential role of age-related telomere uncapping in arterial inflammation. Telomere uncapping, measured by p-histone γ-H2A.X (ser139) localized to telomeres (chromatin immunoprecipitation; ChIP), and telomeric repeat binding factor 2 bound to telomeres (ChIP) was greater in arteries from older adults compared with those from younger adults. There was greater tumor suppressor protein p53 (P53)/cyclin-dependent kinase inhibitor 1A (P21)-induced senescence, measured by P53 bound to P21 gene promoter (ChIP), and greater expression of P21, interleukin 8, and monocyte chemotactic protein 1 mRNA (RT-PCR) in arteries from older adults compared with younger adults. Telomere uncapping was a highly influential covariate for the age-group difference in P53/P21-induced senescence. Despite progressive age-related telomere shortening in human arteries, mean telomere length was not associated with telomere uncapping or P53/P21-induced senescence. Collectively, these findings demonstrate that advancing age is associated with greater telomere uncapping in arteries, which is linked to P53/P21-induced senescence independent of telomere shortening.

  2. Impaired defense of core temperature in aged humans during mild cold stress.

    PubMed

    Degroot, David W; Kenney, W Larry

    2007-01-01

    Aged humans often exhibit an impaired defense of core temperature during cold stress. However, research documenting this response has typically used small subject samples and strong cold stimuli. The purpose of this study was to determine the responses of young and older subjects, matched for anthropometric characteristics, during mild cold stress. Thirty-six young (YS; 23 +/- 1 years, range 18-30) and 46 older (OS; 71 +/- 1 years, range 65-89) subjects underwent a slow transient cold air exposure from a thermoneutral baseline, during which esophageal (T(es)) and mean skin temperatures (T(sk)), O(2) consumption, and skin blood flow (SkBF; laser-Doppler flowmetry) were measured. Cold exposure was terminated at the onset of visible sustained shivering. Net metabolic heat production (M(net)), heat debt, predicted change in midregion temperature (DeltaT(mid)), and tissue insulation (I(t)) were calculated. Cutaneous vascular conductance (CVC) was calculated as laser-Doppler flux/mean arterial pressure and expressed as percent change from baseline (DeltaCVC(%base)). There were no baseline group differences for T(es), but OS M(net) was lower (OS: 38.0 +/- 1.1; YS: 41.9 +/- 1.1 W . m(-2), P < 0.05). T(es) was well maintained in YS but fell progressively in OS (P < 0.01 for all timepoints after 35 min). The skin vasoconstrictor response to mild cold stress was attenuated in OS (42 +/- 3 vs. 53 +/- 4 DeltaCVC(%base), P < 0.01). There were no group differences for T(sk) or I(t), while M(net) remained lower in OS (P < 0.05). The DeltaT(mid) did not account for the drop in T(es) in OS. Healthy aged humans failed to maintain T(es); however, the mechanisms underlying this response are not clear.

  3. Emphysema Distribution and Diffusion Capacity Predict Emphysema Progression in Human Immunodeficiency Virus Infection

    PubMed Central

    Leung, Janice M; Malagoli, Andrea; Santoro, Antonella; Besutti, Giulia; Ligabue, Guido; Scaglioni, Riccardo; Dai, Darlene; Hague, Cameron; Leipsic, Jonathon; Sin, Don D.; Man, SF Paul; Guaraldi, Giovanni

    2016-01-01

    Background Chronic obstructive pulmonary disease (COPD) and emphysema are common amongst patients with human immunodeficiency virus (HIV). We sought to determine the clinical factors that are associated with emphysema progression in HIV. Methods 345 HIV-infected patients enrolled in an outpatient HIV metabolic clinic with ≥2 chest computed tomography scans made up the study cohort. Images were qualitatively scored for emphysema based on percentage involvement of the lung. Emphysema progression was defined as any increase in emphysema score over the study period. Univariate analyses of clinical, respiratory, and laboratory data, as well as multivariable logistic regression models, were performed to determine clinical features significantly associated with emphysema progression. Results 17.4% of the cohort were emphysema progressors. Emphysema progression was most strongly associated with having a low baseline diffusion capacity of carbon monoxide (DLCO) and having combination centrilobular and paraseptal emphysema distribution. In adjusted models, the odds ratio (OR) for emphysema progression for every 10% increase in DLCO percent predicted was 0.58 (95% confidence interval [CI] 0.41–0.81). The equivalent OR (95% CI) for centrilobular and paraseptal emphysema distribution was 10.60 (2.93–48.98). Together, these variables had an area under the curve (AUC) statistic of 0.85 for predicting emphysema progression. This was an improvement over the performance of spirometry (forced expiratory volume in 1 second to forced vital capacity ratio), which predicted emphysema progression with an AUC of only 0.65. Conclusion Combined paraseptal and centrilobular emphysema distribution and low DLCO could identify HIV patients who may experience emphysema progression. PMID:27902753

  4. Being human in a global age of technology.

    PubMed

    Whelton, Beverly J B

    2016-01-01

    This philosophical enquiry considers the impact of a global world view and technology on the meaning of being human. The global vision increases our awareness of the common bond between all humans, while technology tends to separate us from an understanding of ourselves as human persons. We review some advances in connecting as community within our world, and many examples of technological changes. This review is not exhaustive. The focus is to understand enough changes to think through the possibility of healthcare professionals becoming cyborgs, human-machine units that are subsequently neither human and nor machine. It is seen that human technology interfaces are a different way of interacting but do not change what it is to be human in our rational capacities of providing meaningful speech and freely chosen actions. In the highly technical environment of the ICU, expert nurses work in harmony with both the technical equipment and the patient. We used Heidegger to consider the nature of equipment, and Descartes to explore unique human capacities. Aristotle, Wallace, Sokolowski, and Clarke provide a summary of humanity as substantial and relational.

  5. Aging and human sexual behavior: biocultural perspectives - a mini-review.

    PubMed

    Gray, Peter B; Garcia, Justin R

    2012-01-01

    In this mini-review, we consider an evolutionary biocultural perspective on human aging and sexuality. An evolutionary approach to senescence highlights the energetic trade-offs between fertility and mortality. By comparing humans to other primates, we situate human senescence as an evolutionary process, with shifts in postreproductive sexual behavior in this light. Age-related declines in sexual behavior are typical for humans but also highly contingent on the sociocultural context within which aging individuals express their sexuality. We briefly review some of the most comprehensive studies of aging and sexual behavior, both from the USA and cross-culturally. We frame these patterns with respect to the long-term relationships within which human sexual behavior typically occurs. Because sexuality is typically expressed within pair-bonds, sexual behavior sometimes declines in both members of a couple with age, but also exhibits sex-specific effects that have their roots in evolved sex differences.

  6. Cardiac and renal function are progressively impaired with aging in Zucker diabetic fatty type II diabetic rats.

    PubMed

    Baynes, John; Murray, David B

    2009-01-01

    This study investigated the temporal relationship between cardiomyopathy and renal pathology in the type II diabetic Zucker diabetic fatty (ZDF) rat. We hypothesized that changes in renal function will precede the development of cardiac dysfunction in the ZDF rat. Animals (10 weeks old) were divided into four experimental groups: Lean Control (fa/?) LC(n = 7), untreated ZDF rats (n = 7) sacrificed at 16 weeks of age, and LC (n = 7) untreated ZDF rats (n = 9) sacrificed at 36 weeks of age. LV structural/functional parameters were assessed via Millar conductance catheter. Renal function was evaluated via markers of proteinuria and evidence of hydronephrosis. LV mass was significantly less in the ZDF groups at both time points compared to age-matched LC. End diastolic volume was increased by 16% at 16 weeks and by 37% at 36 weeks of age (p < 0.05 vs. LC). End diastolic pressure and end systolic volume were significantly increased (42% and 27%respectively) at 36 weeks of age in the ZDF compared to LC. Kidney weights were significantly increased at both 16 and 36 week in ZDF animals (p < 0.05 vs. LC). Increased urinary albumin and decreased urinary creatinine were paralleled by a marked progression in the severity of hydronephrosis from 16 to 36 weeks of age in the ZDF group. In summary, there is evidence of progressive structural and functional changes in both the heart and kidney, starting as early as 16 weeks,without evidence that one pathology precedes or causes the other in the ZDF model of type II diabetes.

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

    PubMed Central

    Leggett, R W

    1993-01-01

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

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

    PubMed

    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.

  9. Evolution of Human Rights in the Age of Biotechnology.

    ERIC Educational Resources Information Center

    Hron, Benjamin

    1998-01-01

    Considers how biotechnology affects human-rights issues; in particular, the need for reexamining concerns about reproductive technology, the rights of indigenous peoples, and the rights of future generations. Maintains that the new areas for human-rights discussions, such as germ-line manipulation and genetic screening, are unprecedented concerns…

  10. Human gut microbiome viewed across age and geography

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, we characterized bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy child...

  11. Progression in High School Students' (Aged 16-18) Conceptualizations about Chemical Reactions in Solution.

    ERIC Educational Resources Information Center

    Boo, Hong-Kwen; Watson, J. R.

    2001-01-01

    Explores the development over time of students' understandings of the concept of chemical reaction in the context of two familiar reactions in solution. Based on interviews (n=48), results show that students made some progress in their understanding of the concept of chemical reaction but some fundamental misconceptions remained. (Author/MM)

  12. [Age-dependent morphology of human pineal gland: supravital study].

    PubMed

    Ivanov, S V

    2007-01-01

    On the base of analysis of 5784 events of diagnostic magnetic-resonance tomography studies of the head of patients in radio diagnosis departments the database is formed. Only events (n=411) without cerebral, oncology, endocrine and other pathology are taken in database. The material was grouped to time and date of the study, sex and age in accordance with generally accepted categorization. Maximum linear sizes of pineal gland and hypophysis cerebri in sagittal, axial and coronar projection were measured in all events; volumes of the organs were calculated on the formula of a ball. It is defined that the volume of pineal gland increases from birth till 17-21 year age, gradually falls till the second mature age and is getting stable in old age. The normative factors of the volume of pineal gland and hypophysis cerebri for 8 age groups are determined. "Brain sand" and false cysts in pineal gland can be observed in all age groups. The petrification degree of pineal gland, as of computer tomography, varies from 30 to 277 ed. HV. For the factor of pineal gland volume and factor of cysts frequency in pineal gland a puberty "collapse" is typical, mainly in men.

  13. Epigenomic maintenance through dietary intervention can facilitate DNA repair process to slow down the progress of premature aging.

    PubMed

    Ghosh, Shampa; Sinha, Jitendra Kumar; Raghunath, Manchala

    2016-09-01

    DNA damage caused by various sources remains one of the most researched topics in the area of aging and neurodegeneration. Increased DNA damage causes premature aging. Aging is plastic and is characterised by the decline in the ability of a cell/organism to maintain genomic stability. Lifespan can be modulated by various interventions like calorie restriction, a balanced diet of macro and micronutrients or supplementation with nutrients/nutrient formulations such as Amalaki rasayana, docosahexaenoic acid, resveratrol, curcumin, etc. Increased levels of DNA damage in the form of double stranded and single stranded breaks are associated with decreased longevity in animal models like WNIN/Ob obese rats. Erroneous DNA repair can result in accumulation of DNA damage products, which in turn result in premature aging disorders such as Hutchinson-Gilford progeria syndrome. Epigenomic studies of the aging process have opened a completely new arena for research and development of drugs and therapeutic agents. We propose here that agents or interventions that can maintain epigenomic stability and facilitate the DNA repair process can slow down the progress of premature aging, if not completely prevent it. © 2016 IUBMB Life, 68(9):717-721, 2016.

  14. Modulation of Different Human Immunodeficiency Virus Type 1 Nef Functions during Progression to AIDS

    PubMed Central

    Carl, Silke; Greenough, Thomas C.; Krumbiegel, Mandy; Greenberg, Michael; Skowronski, Jacek; Sullivan, John L.; Kirchhoff, Frank

    2001-01-01

    The human immunodeficiency virus type 1 (HIV-1) Nef protein has several independent functions that might contribute to efficient viral replication in vivo. Since HIV-1 adapts rapidly to its host environment, we investigated if different Nef properties are associated with disease progression. Functional analysis revealed that nef alleles obtained during late stages of infection did not efficiently downmodulate class I major histocompatibility complex but were highly active in the stimulation of viral replication. In comparison, functional activity in downregulation of CD4 and enhancement of HIV-1 infectivity were maintained or enhanced after AIDS progression. Our results demonstrate that various Nef activities are modulated during the course of HIV-1 infection to maintain high viral loads at different stages of disease progression. These findings suggest that all in vitro Nef functions investigated contribute to AIDS pathogenesis and indicate that nef variants with increased pathogenicity emerge in a significant number of HIV-1-infected individuals. PMID:11264355

  15. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    SciTech Connect

    Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  16. Effects of aging on basal fat oxidation in obese humans.

    PubMed

    Solomon, Thomas P J; Marchetti, Christine M; Krishnan, Raj K; Gonzalez, Frank; Kirwan, John P

    2008-08-01

    Basal fat oxidation decreases with age. In obesity, it is not known whether this age-related process occurs independently of changes in body composition and insulin sensitivity. Therefore, body composition, resting energy expenditure, basal substrate oxidation, and maximal oxygen consumption (VO(2)max) were measured in 10 older (age, 60 +/- 4 years; mean +/- SEM) and 10 younger (age, 35 +/- 4 years) body mass index-matched, obese, normal glucose-tolerant individuals. Fasting blood samples were also collected. Older subjects had slightly elevated fat mass (32.2 +/- 7.1 vs 36.5 +/- 6.7 kg, P = .16); however, waist circumference was not different between groups (104.3 +/- 10.3 vs 102.1 +/- 12.6 cm, P = .65). Basal fat oxidation was 22% lower (1.42 +/- 0.14 vs 1.17 +/- 0.22 mg/kg fat-free mass per minute, P = .03) in older subjects. The VO(2)max was also decreased in older individuals (44.6 +/- 7.1 vs 38.3 +/- 6.0 mL/kg fat-free mass per minute, P = .03); but insulin sensitivity, lipemia, and leptinemia were not different between groups (P > .05). Fat oxidation was most related to age (r = -0.61, P = .003) and VO(2)max (r = 0.52, P = .01). These data suggest that aging per se is responsible for reduced basal fat oxidation and maximal oxidative capacity in older obese individuals, independent of changes in insulin resistance, body mass, and abdominal fat. This indicates that age, in addition to obesity, is an independent risk factor for weight gain and for the metabolic complications of elevated body fat.

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  18. Genetic Determinants of Human Health Span and Life Span: Progress and New Opportunities

    PubMed Central

    Martin, George M; Bergman, Aviv; Barzilai, Nir

    2007-01-01

    We review three approaches to the genetic analysis of the biology and pathobiology of human aging. The first and so far the best-developed is the search for the biochemical genetic basis of varying susceptibilities to major geriatric disorders. These include a range of progeroid syndromes. Collectively, they tell us much about the genetics of health span. Given that the major risk factor for virtually all geriatric disorders is biological aging, they may also serve as markers for the study of intrinsic biological aging. The second approach seeks to identify allelic contributions to exceptionally long life spans. While linkage to a locus on Chromosome 4 has not been confirmed, association studies have revealed a number of significant polymorphisms that impact upon late-life diseases and life span. The third approach remains theoretical. It would require longitudinal studies of large numbers of middle-aged sib-pairs who are extremely discordant or concordant for their rates of decline in various physiological functions. We can conclude that there are great opportunities for research on the genetics of human aging, particularly given the huge fund of information on human biology and pathobiology, and the rapidly developing knowledge of the human genome. PMID:17677003

  19. Progressive post-yield behavior of human cortical bone in shear

    PubMed Central

    Dong, Xuanliang N.; Luo, Qing; Wang, Xiaodu

    2012-01-01

    Bone fragility depends on its post-yield behavior since most of energy dissipation in bone occurs during the post-yield deformation. Previous studies have investigated the progressive changes in the post-yield behavior of human cortical bone in tension and compression using a novel progressive loading scheme. However, little is known regarding the progressive changes in the post-yield behavior of bone in shear. The objective of this short study was to address this issue by testing bone specimens in an inclined double notch shear configuration using the progressive loading protocol. The results of this study indicated that the shear modulus of bone decreased with respect to the applied strain, and the rate of degradation was about 50% less than those previously observed in compression and tension tests. In addition, a quasi-linear relationship between the plastic and applied strains was observed in shear mode, which is similar to those previously reported in tension and compression tests. However, the viscous responses of bone (i.e. relaxation time constants and stress magnitude) demonstrated slight differences in shear compared with those observed in tension and compression tests. Nonetheless, the results of this study suggest that the intrinsic mechanism of plastic deformation of human cortical bone may be independent of loading modes. PMID:23219946

  20. From Oxford to Hawaii Ecophysiological Barriers Limit Human Progression in Ten Sport Monuments

    PubMed Central

    Desgorces, François-Denis; Berthelot, Geoffroy; El Helou, Nour; Thibault, Valérie; Guillaume, Marion; Tafflet, Muriel; Hermine, Olivier; Toussaint, Jean-François

    2008-01-01

    In order to understand the determinants and trends of human performance evolution, we analyzed ten outdoor events among the oldest and most popular in sports history. Best performances of the Oxford-Cambridge boat race (since 1836), the channel crossing in swimming (1875), the hour cycling record (1893), the Elfstedentocht speed skating race (1909), the cross country ski Vasaloppet (1922), the speed ski record (1930), the Streif down-hill in Kitzbühel (1947), the eastward and westward sailing transatlantic records (1960) and the triathlon Hawaii ironman (1978) all follow a similar evolutive pattern, best described through a piecewise exponential decaying model (r2 = 0.95±0.07). The oldest events present highest progression curvature during their early phase. Performance asymptotic limits predicted from the model may be achieved in fourty years (2049±32 y). Prolonged progression may be anticipated in disciplines which further rely on technology such as sailing and cycling. Human progression in outdoor sports tends to asymptotic limits depending on physiological and environmental parameters and may temporarily benefit from further technological progresses. PMID:18985149

  1. Dietary restriction, mitochondrial function and aging: from yeast to humans

    PubMed Central

    Ruetenik, Andrea; Barrientos, Antoni

    2015-01-01

    SUMMARY Dietary restriction (DR) attenuates many detrimental effects of aging and consequently promotes health and increases longevity across organisms. While over the last 15 years extensive research has been devoted towards understanding the biology of aging, the precise mechanistic aspects of DR are yet to be settled. Abundant experimental evidence indicates that the DR effect on stimulating health impinges several metabolic and stress-resistance pathways. Downstream effects of these pathways include a reduction in cellular damage induced by oxidative stress, enhanced efficiency of mitochondrial functions and maintenance of mitochondrial dynamics and quality control, thereby attenuating age-related declines in mitochondrial function. However, the literature also accumulates conflicting evidence regarding how DR ameliorates mitochondrial performance and whether that is enough to slow age-dependent cellular and organismal deterioration. Here, we will summarize the current knowledge about how and to which extent the influence of different DR regimes on mitochondrial biogenesis and function contribute to postpone the detrimental effects of aging on healthspan and lifespan. PMID:25979234

  2. The Membrane Attack Complex in Aging Human Choriocapillaris

    PubMed Central

    Mullins, Robert F.; Schoo, Desi P.; Sohn, Elliott H.; Flamme-Wiese, Miles J.; Workamelahu, Grefachew; Johnston, Rebecca M.; Wang, Kai; Tucker, Budd A.; Stone, Edwin M.

    2015-01-01

    Age-related macular degeneration (AMD) is a common disease that can result in severe visual impairment. Abnormal regulation of the complement system has been implicated in its pathogenesis, and CFH polymorphisms contribute substantially to risk. How these polymorphisms exert their effects is poorly understood. We performed enzyme-linked immunosorbent assay (ELISA) analysis on young, aged, and AMD choroids to determine the abundance of the membrane attack complex (MAC) and performed immunofluorescence studies on eyes from 117 donors to evaluate the MAC in aging, early AMD, and advanced AMD. Morphometric studies were performed on eyes with high- or low-risk CFH genotypes. ELISA confirmed that MAC increases significantly with aging and with AMD. MAC was localized to Bruch’s membrane and the choriocapillaris and was detectable at low levels as early as 5 years of age. Hard drusen were labeled with anti-MAC antibody, but large or confluent drusen and basal deposits were generally unlabeled. Labeling of retinal pigment epithelium was observed in some cases of advanced AMD, but not in early disease. Eyes homozygous for the high-risk CFH genotype had thinner choroids than low-risk homozygotes (P < 0.05). These findings suggest that increased complement activation in AMD and in high-risk genotypes can lead to loss of endothelial cells in early AMD. Treatments to protect the choriocapillaris in early AMD are needed. PMID:25204844

  3. Sympathetic control of reflex cutaneous vasoconstriction in human aging

    PubMed Central

    Alexander, Lacy M.; Kenney, W. Larry

    2015-01-01

    This Synthesis highlights a series of recent studies that has systematically interrogated age-related deficits in cold-induced skin vasoconstriction. In response to cold stress, a reflex increase in sympathetic nervous system activity mediates reductions in skin blood flow. Reflex vasoconstriction during cold exposure is markedly impaired in aged skin, contributing to the relative inability of healthy older adults to maintain core temperature during mild cold stress in the absence of appropriate behavioral thermoregulation. This compromised reflex cutaneous vasoconstriction in healthy aging can occur as a result of functional deficits at multiple points along the efferent sympathetic reflex axis, including blunted sympathetic outflow directed to the skin vasculature, reduced presynaptic neurotransmitter synthesis and/or release, and altered end-organ responsiveness at several loci, in addition to potential alterations in afferent thermoreceptor function. Arguments have been made that the relative inability of aged skin to appropriately constrict is due to the aging cutaneous arterioles themselves, whereas other data point to the neural circuitry controlling those vessels. The argument presented herein provides strong evidence for impaired efferent sympathetic control of the peripheral cutaneous vasculature during whole body cold exposure as the primary mechanism responsible for attenuated vasoconstriction. PMID:26272321

  4. Similarity between humans and foams in aging dynamics

    NASA Astrophysics Data System (ADS)

    Weon, Byung Mook; Stewart, Peter S.

    2014-03-01

    Foams are cellular networks between two immiscible phases. Foams are initially unstable and finally evolve toward a state of lower energy through sequential coalescences of bubbles. In physics, foams are model systems for materials that minimize surface energy. We study coalescence dynamics of clean foams using numerical simulations with a network model. Initial clean foams consist of equally pressurized bubbles and a low fraction of liquid films without stabilizing agents. Aging of clean foams occurs with time as bubbles rapidly coalesce by film rupture and finally evolve toward a new quasi-equilibrium state. Here we find that foam aging is analogous to biological aging: the death rate of bubbles increases exponentially with time, which is similar to the Gompertz mortality law for biological populations. The coalescence evolution of foams is self-similar regardless of initial conditions. The population change of bubbles is well described by a Boltzmann sigmoidal function, indicating that the foam aging is a phase transition phenomenon. This result suggests that foams can be useful model systems for giving insights into biological aging. Suwon 440-746, South Korea.

  5. Sympathetic control of reflex cutaneous vasoconstriction in human aging.

    PubMed

    Greaney, Jody L; Alexander, Lacy M; Kenney, W Larry

    2015-10-01

    This Synthesis highlights a series of recent studies that has systematically interrogated age-related deficits in cold-induced skin vasoconstriction. In response to cold stress, a reflex increase in sympathetic nervous system activity mediates reductions in skin blood flow. Reflex vasoconstriction during cold exposure is markedly impaired in aged skin, contributing to the relative inability of healthy older adults to maintain core temperature during mild cold stress in the absence of appropriate behavioral thermoregulation. This compromised reflex cutaneous vasoconstriction in healthy aging can occur as a result of functional deficits at multiple points along the efferent sympathetic reflex axis, including blunted sympathetic outflow directed to the skin vasculature, reduced presynaptic neurotransmitter synthesis and/or release, and altered end-organ responsiveness at several loci, in addition to potential alterations in afferent thermoreceptor function. Arguments have been made that the relative inability of aged skin to appropriately constrict is due to the aging cutaneous arterioles themselves, whereas other data point to the neural circuitry controlling those vessels. The argument presented herein provides strong evidence for impaired efferent sympathetic control of the peripheral cutaneous vasculature during whole body cold exposure as the primary mechanism responsible for attenuated vasoconstriction.

  6. Human aging compromises attentional control of auditory perception.

    PubMed

    Passow, Susanne; Westerhausen, René; Wartenburger, Isabell; Hugdahl, Kenneth; Heekeren, Hauke R; Lindenberger, Ulman; Li, Shu-Chen

    2012-03-01

    Older adults often experience hearing difficulties in multitalker situations. Attentional control of auditory perception is crucial in situations where a plethora of auditory inputs compete for further processing. We combined an intensity-modulated dichotic listening paradigm with attentional manipulations to study adult age differences in the interplay between perceptual saliency and attentional control of auditory processing. When confronted with two competing sources of verbal auditory input, older adults modulated their attention less flexibly and were more driven by perceptual saliency than younger adults. These findings suggest that aging severely impairs the attentional regulation of auditory perception.

  7. Gaps in the evidence about companion animals and human health: some suggestions for progress.

    PubMed

    Chur-Hansen, Anna; Stern, Cindy; Winefield, Helen

    2010-09-01

    A number of researchers have explored the relationship between companion animal ownership and human physical and psychological health. Results have been inconclusive, with positive, neutral and negative effects variously reported in the literature. Furthermore, the possible mechanisms of any influence are frustratingly unclear. A number of conceptual and methodological weaknesses have hampered progress in our understanding of how companion animals may impact upon human health. The two evidence gaps discussed in this paper, with suggestions for needed next steps, are: (i) a preponderance of anecdotal reports and cross-sectional research designs; and (ii) failure to control for a host of other known influences on human health including health habits, level of attachment to the companion animal and human social supports. Finally, an example of these gaps is provided in relation to the literature on the effects of animals on elderly nursing home residents.

  8. Lower expression of Nrdp1 in human glioma contributes tumor progression by reducing apoptosis.

    PubMed

    Shi, Hengliang; Du, Jin; Wang, Lei; Zheng, Bao; Gong, Hui; Wu, Yuxuan; Tang, Yuan; Gao, Yong; Yu, Rutong

    2014-10-01

    Ubiquitin ligase Nrdp1 (neuregulin receptor degradation protein 1) plays important roles in multiple physiological process because it can ubiquitinate various substrates such as ErbB3, BRUCE, MyD88, C/EBPβ, and Parkin, and so forth. In addition to the physiological function, it was also found to be involved in tumor progression. It has been shown that loss of Nrdp1 enhances breast cancer cell growth. Up to now, the role of Nrdp1 in glioma has not been elucidated. Here, we reported that Nrdp1 as well as cleaved caspase 3 was lower expressed in human glioma tissues comparing with the nontumorous. And then we found that the expression of Nrdp1 and cleaved caspase 3 was increased in the treatment of Temozolomide (TMZ), a drug for glioma chemotherapy. Further investigation indicated that transient transfection of Nrdp1 significantly promoted cell apoptosis by aggravating the degradation of BRUCE and activation of caspase 3. In addition, overexpression of Nrdp1 augmented TMZ induced apoptosis by evaluating the degradation of BRUCE and the activation of caspase 3, while silencing of Nrdp1 reduced the sensitivity to the TMZ by inhibiting the degradation of BRUCE and the activation of caspase 3 in human glioma cells. These observations show that Nrdp1 is a pro-apoptotic protein in human glioma and lower expression of Nrdp1 in human glioma may promote tumor progression by reducing apoptosis, suggesting that Nrdp1 may be an important regulator in the development of human glioma.

  9. EFFECTS OF AGE, DIETARY AND BEHAVIORAL ENRICHMENT ON BRAIN MITOCHONDRIA IN A CANINE MODEL OF HUMAN AGING

    PubMed Central

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

    2009-01-01

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

  10. In the rush for green gold: Can green tea delay age-progressive brain neurodegeneration?

    PubMed

    Mandel, Silvia A; Youdim, Moussa B H

    2012-12-01

    It is evident that brain aging engages changes in biological systems linked to synaptic function and cell metabolism and in the capacity to cope with different stresses that are either idiopathic in nature, or subject to environmental insults. In a substantial segment of the aging population there is a pathological transition to cognitive and behavioral dysfunction and thus, age constitutes the primary risk factor for Alzheimer's disease and other neurodegenerative disorders. To address the etiological complexity of aging and age-associated conditions, a new paradigm gaining increasing acceptance considers the use of multi-targeted ligands or combination of drugs to modulate several targets at once. During the past years intensive efforts are dedicated to the implementation of life style habits such as exercise and dietary compounds/supplements in combination with symptomatic treatment drugs to improve age-related cognitive decline and to attenuate motor and neurological dysfunction in neurodegenerative diseases. The catechin polyphenols constituents of green tea, which were for long time regarded merely as dietary antioxidants, have caught our and other scientist's attention because of their diverse pharmacological activities, which have been allied to a possible beneficial action on brain health. This review will elaborate on the impact of nutritional supplementation on brain function in general, and provide a compilation of the most updated literature on epidemiology, clinical and animal studies with green tea polyphenols in age-associated cognitive decline and in fighting neurodegenerative diseases. To conclude, a future perspective on the utility and assigned patents with green tea constituents will be presented.

  11. Research Progress on the Risk Factors and Outcomes of Human Carotid Atherosclerotic Plaques

    PubMed Central

    Xiong, Xiang-Dong; Xiong, Wei-Dong; Xiong, Shang-Shen; Chen, Gui-Hai

    2017-01-01

    Objective: Atherosclerosis is an inflammatory process that results in complex lesions or plaques that protrude into the arterial lumen. Carotid atherosclerotic plaque rupture, with distal atheromatous debris embolization, causes cerebrovascular events. This review aimed to explore research progress on the risk factors and outcomes of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention. Data Sources: We searched the PubMed database for recently published research articles up to June 2016, with the key words of “risk factors”, “outcomes”, “blood components”, “molecular mechanisms”, “cellular mechanisms”, and “human carotid atherosclerotic plaques”. Study Selection: The articles, regarding the latest developments related to the risk factors and outcomes, atherosclerotic plaque composition, blood components, and consequences of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention, were selected. Results: This review described the latest researches regarding the interactive effects of both traditional and novel risk factors for human carotid atherosclerotic plaques, novel insights into human carotid atherosclerotic plaque composition and blood components, and consequences of human carotid atherosclerotic plaque. Conclusion: Carotid plaque biology and serologic biomarkers of vulnerability can be used to predict the risk of cerebrovascular events. Furthermore, plaque composition, rather than lesion burden, seems to most predict rupture and subsequent thrombosis. PMID:28303857

  12. Explaining Tristan-Gough Plume Dynamics with New Age Data from Multiple Age-Progressive Seamount Sub-Tracks in the Young Walvis Ridge Guyot Province

    NASA Astrophysics Data System (ADS)

    Schnur, S.; Koppers, A. A. P.; Class, C.; Sager, W. W.

    2014-12-01

    Together, the Etendeka flood basalt province of Namibia, the old Walvis Ridge and the young Walvis Ridge guyot province constitute a 130 Myr record of hotspot volcanism in the South Atlantic. Previous age-dating along the Walvis Ridge has revealed a strong linear age progression (~30 mm/a, Rohde et al. 2013) that is consistent with modeled relative spreading rates between the African and South American plates (~33 mm/a over the past 3 Myr, NUVEL-1 model). However, tracing the path of the African plate over the Tristan-Gough hotspot is more complicated in the guyot province because the seamounts do not form a single trail. Instead we see a region of diffuse volcanism with multiple discontinuous linear sub-tracks of seamounts and coeval volcanism at edifices located up to 400 km apart. We present here the results of 24 new 40Ar/39Ar step-heating experiments on groundmass and phenocryst separates from trachybasalts, trachy-andesites, trachytes and similarly evolved rocks dredged from the guyot province in 2012. The age-dating results represent nine seamounts in the southern half of the guyot province, most of which have never been studied before. We will combine the new ages with previous high-resolution ages from nearby seamounts to constrain plate motion rates recorded by each of the sub-tracks. We will compare the results with previously-established absolute plate motion models in order to shed light on the relationship between plume dynamics and the unusual spatial distribution of volcanism in this region.

  13. Reliability and factorial validity of the standard progressive matrices among Kuwaiti children ages 8 to 15 years.

    PubMed

    Abdel-Khalek, Ahmed M

    2005-10-01

    The Raven Standard Progressive Matrices was administered to a sample of 6,529 children in Kuwait ranging in age from 8 to 15 years. Test-retest reliability (N = 968) ranged between .69 and .85, while Cronbach coefficients alpha ranged from .88 to .93, showing from acceptable to good temporal stability and from good to high internal consistency. The loadings of the five sets of matrices on the only salient factor ranged from .73 to .89 indicating the good factorial validity of the scale. The rtest seems useful in the Kuwaiti context.

  14. Assessing Progress towards Public Health, Human Rights, and International Development Goals Using Frontier Analysis

    PubMed Central

    Luh, Jeanne; Cronk, Ryan; Bartram, Jamie

    2016-01-01

    Indicators to measure progress towards achieving public health, human rights, and international development targets, such as 100% access to improved drinking water or zero maternal mortality ratio, generally focus on status (i.e., level of attainment or coverage) or trends in status (i.e., rates of change). However, these indicators do not account for different levels of development that countries experience, thus making it difficult to compare progress between countries. We describe a recently developed new use of frontier analysis and apply this method to calculate country performance indices in three areas: maternal mortality ratio, poverty headcount ratio, and primary school completion rate. Frontier analysis is used to identify the maximum achievable rates of change, defined by the historically best-performing countries, as a function of coverage level. Performance indices are calculated by comparing a country’s rate of change against the maximum achievable rate at the same coverage level. A country’s performance can be positive or negative, corresponding to progression or regression, respectively. The calculated performance indices allow countries to be compared against each other regardless of whether they have only begun to make progress or whether they have almost achieved the target. This paper is the first to use frontier analysis to determine the maximum achievable rates as a function of coverage level and to calculate performance indices for public health, human rights, and international development indicators. The method can be applied to multiple fields and settings, for example health targets such as cessation in smoking or specific vaccine immunizations, and offers both a new approach to analyze existing data and a new data source for consideration when assessing progress achieved. PMID:26812524

  15. Aging process of myelinated nerve fibers in the human Lissauer tract.

    PubMed

    Motoura, Hiroyuki; Goto, Noboru; Goto, Jun; Ezure, Hiromitsu; Shibata, Masakazu

    2005-03-01

    We calculated numbers and axonal areas of myelinated nerve fibers in the Lissauer tract of the human lumbar spinal cord (L1) from the viewpoint of the aging process. We examined 20 human spinal cords from 13 males and 7 females, age ranging from 41 to 88 years old. We found that, although the number of nerve fibers showed no significant change in relation to the age of the subject, the axonal area of myelinated nerve fiber in the Lissauer tract did decrease with age.

  16. "Clever Microbes": bacteriology and sanitary technology in Manchester and Chicago during the progressive age.

    PubMed

    Platt, Harold L

    2004-01-01

    A neglected aspect of the history of germ theories is its use in the purification of sewage. In the 1890s, progressive reformers rapidly developed bacteriological methods of wastewater treatment. A comparison of the United Kingdom's Manchester and the United States' Chicago shows, however, that science and technology were mediated by political culture and institutions. In Manchester, a politics of deference and strong extralocal government gave the authority of scientific expertise a decisive role in policy formation. In Chicago, devolution of power to the ward bosses meant a quarter-century of defiance against the national authority and its effort to get the city to install a modern sanitation system.

  17. First rib metamorphosis: its possible utility for human age-at-death estimation.

    PubMed

    Kunos, C A; Simpson, S W; Russell, K F; Hershkovitz, I

    1999-11-01

    Human first ribs demonstrate predictable, sequential changes in shape, size, and texture with increasing age, and thus, can be used as an indicator of age at death. Metamorphosis of the first rib's head, tubercle, and costal face was documented in a cross-sectional sample of preadult and adult first ribs of known age at death from the Hamann-Todd skeletal collection (Cleveland Museum of Natural History, Cleveland, Ohio). Blind tests of the usefulness of the first rib as an age indicator were conducted, including tabulation of intraobserver and interobserver inaccuracies and biases. First rib age estimates show inaccuracies and biases by decade comparable to those generated by other aging techniques. Indeed, the first rib method is useful as an isolated age indicator. When used in conjunction with other age indicators, the first rib improves the quality of summary age assessments.

  18. The evolution of human periodontal tissues with ageing.

    PubMed

    Craca, R; Romagnoli, P; Cambi, S; Orlando, S

    1991-01-01

    In this research, the structural modifications with ageing of clinically healthy periodontal tissues were analyzed by means of polarization microscopy and morphometrical methods for light microscopy. The new findings may be summarized as follows. The periodontal ligament was found to be widened in the cervical and apical regions. The thickening of cementum with ageing was shown to be accompanied by a modification in the shape of Sharpey's fibres, which in the elderlies were wavy instead of straight as in the control. Lamellar bone, forming an osteone, was found to substitute in part for cementum in one tooth. These results are interpreted as indicating that: (1) late active eruption occurs in man, causing the observed modification in the thickness of periodontal ligament and cementum in the apical region and in the direction of Sharpey's fibres within cementum; (2) cementum may undergo renewal during lifetime and in this case bone may be deposited in contact with dentin.

  19. Immunoglobulin patterns in humans over 95 years of age.

    PubMed Central

    Radl, J; Sepers, J M; Skvaril, F; Morell, A; Hijmans, W

    1975-01-01

    Immunoglobulin patterns were investigated in seventy-three volunteers older than 95 years. An idiopathic paraproteinaemia was found in 19% of the cases. A restriction of heterogeneity and an imbalance in the kappa/lambda ratio of the immunoglobulins was seen in a number of other sera. Determinations of immunoglobulin levels in sera of individuals without paraproteinaemia showed an increase in IgA and IgG. The quantitations of the IgG subclasses demonstrated that an increase in the IgG1 and IgG3 subclasses is responsible for the elevated level of the IgG. The variation in the immunoglobulin levels increased significantly with age of IgM and for the three major IgG subclasses. No abnormalities were found in the urine or in the mixed saliva. These results indicate that selective changes in the extent of the antibody-immunoglobulin repertoire characterize the immunoglobulin pattern of ageing man. PMID:1212818

  20. A review of the equine age-related changes in the immune system: comparisons between human and equine aging, with focus on lung-specific immune-aging.

    PubMed

    Hansen, S; Baptiste, K E; Fjeldborg, J; Horohov, D W

    2015-03-01

    The equine aging process involves many changes to the immune system that may be related to genetics, the level of nutrition, the environment and/or an underlying subclinical disease. Geriatric horses defined as horses above the age of 20, exhibit a decline in body condition, muscle tone and general well-being. It is not known whether these changes contribute to decreased immune function or are the result of declining immune function. Geriatric years are characterized by increased susceptibility to infections and a reduced antibody response to vaccination as a result of changes in the immune system. Humans and horses share many of these age-related changes, with only a few differences. Thus, inflamm-aging and immunosenescence are well-described phenomena in both human and equine research, particularly in relation to the peripheral blood and especially the T-cell compartment. However, the lung is faced with unique challenges because of its constant interaction with the external environment and thus may not share similarities to peripheral blood when considering age-related changes in immune function. Indeed, recent studies have shown discrepancies in cytokine mRNA and protein expression between the peripheral blood and bronchoalveolar lavage immune cells. These results provide important evidence that age-related immune changes or 'dys-functions' are organ-specific.

  1. Royal jelly prevents the progression of sarcopenia in aged mice in vivo and in vitro.

    PubMed

    Niu, Kaijun; Guo, Hui; Guo, Yinting; Ebihara, Satoru; Asada, Masanori; Ohrui, Takashi; Furukawa, Katsutoshi; Ichinose, Masakazu; Yanai, Kazuhiko; Kudo, Yukitsuka; Arai, Hiroyuki; Okazaki, Tatsuma; Nagatomi, Ryoichi

    2013-12-01

    Sarcopenia is characterized by the age-related loss of muscle mass and strength. One of the mechanisms of sarcopenia is the loss in the function and number of muscle satellite cells. Royal jelly (RJ) is a health food used worldwide. To obtain better digestion and absorption than RJ, protease-treated RJ (pRJ) has been developed. RJ and pRJ have been suggested to have potential pharmacological benefits such as prolonging the life span and reducing fatigue. Because these effects may improve sarcopenia and the functions of satellite cells, we examined the effects of RJ or pRJ treatment on the skeletal muscles in an animal model using aged mice. In vivo, RJ/pRJ treatment attenuated the decrease in the muscle weight and grip strength and increased the regenerating capacity of injured muscles and the serum insulin-like growth factor-1 levels compared with controls. In vitro, using isolated satellite cells from aged mice, pRJ treatment increased the cell proliferation rate, promoted cell differentiation, and activated Akt intracellular signaling pathway compared with controls. These findings suggest that RJ/pRJ treatment had a beneficial effect on age-related sarcopenia.

  2. Early Characteristics of Children with ASD Who Demonstrate Optimal Progress between Age Two and Four

    ERIC Educational Resources Information Center

    Moulton, Emily; Barton, Marianne; Robins, Diana L.; Abrams, Danielle N.; Fein, Deborah

    2016-01-01

    Although for many children, Autism Spectrum Disorder (ASD) is a lifelong disability, a subset of children with ASD lose their diagnosis and show typical cognitive and adaptive abilities. The ages at which this transition can occur is not known, but it sometimes occurs quite early. Participants in the current study were 207 children with an ASD at…

  3. Family Economic Hardship and Progression of Poor Mental Health in Middle-Aged Husbands and Wives

    ERIC Educational Resources Information Center

    Wickrama, K. A. S.; Surjadi, Florensia F.; Lorenz, Frederick O.; Conger, Rand D.; O'Neal, Catherine Walker

    2012-01-01

    Using prospective data from 370 middle-aged husbands and wives during a 12-year period, we investigated the intra-individual and dyadic influence of family economic hardship on the levels of depressive symptoms of husbands and wives over their middle years. The results suggest that family economic hardship during the early middle years contributes…

  4. Collagen Fragmentation Promotes Oxidative Stress and Elevates Matrix Metalloproteinase-1 in Fibroblasts in Aged Human Skin

    PubMed Central

    Fisher, Gary J.; Quan, Taihao; Purohit, Trupta; Shao, Yuan; Cho, Moon Kyun; He, Tianyuan; Varani, James; Kang, Sewon; Voorhees, John J.

    2009-01-01

    Aged human skin is fragile because of fragmentation and loss of type I collagen fibrils, which confer strength and resiliency. We report here that dermal fibroblasts express increased levels of collagen-degrading matrix metalloproteinases-1 (MMP-1) in aged (>80 years old) compared with young (21 to 30 years old) human skin in vivo. Transcription factor AP-1 and α2β1 integrin, which are key regulators of MMP-1 expression, are also elevated in fibroblasts in aged human skin in vivo. MMP-1 treatment of young skin in organ culture causes fragmentation of collagen fibrils and reduces fibroblast stretch, consistent with reduced mechanical tension, as observed in aged human skin. Limited fragmentation of three-dimensional collagen lattices with exogenous MMP-1 also reduces fibroblast stretch and mechanical tension. Furthermore, fibroblasts cultured in fragmented collagen lattices express elevated levels of MMP-1, AP-1, and α2β1 integrin. Importantly, culture in fragmented collagen raises intracellular oxidant levels and treatment with antioxidant MitoQ10 significantly reduces MMP-1 expression. These data identify positive feedback regulation that couples age-dependent MMP-1-catalyzed collagen fragmentation and oxidative stress. We propose that this self perpetuating cycle promotes human skin aging. These data extend the current understanding of the oxidative theory of aging beyond a cellular-centric view to include extracellular matrix and the critical role that connective tissue microenvironment plays in the biology of aging. PMID:19116368

  5. Predicting human age using regional morphometry and inter-regional morphological similarity

    NASA Astrophysics Data System (ADS)

    Wang, Xun-Heng; Li, Lihua

    2016-03-01

    The goal of this study is predicting human age using neuro-metrics derived from structural MRI, as well as investigating the relationships between age and predictive neuro-metrics. To this end, a cohort of healthy subjects were recruited from 1000 Functional Connectomes Project. The ages of the participations were ranging from 7 to 83 (36.17+/-20.46). The structural MRI for each subject was preprocessed using FreeSurfer, resulting in regional cortical thickness, mean curvature, regional volume and regional surface area for 148 anatomical parcellations. The individual age was predicted from the combination of regional and inter-regional neuro-metrics. The prediction accuracy is r = 0.835, p < 0.00001, evaluated by Pearson correlation coefficient between predicted ages and actual ages. Moreover, the LASSO linear regression also found certain predictive features, most of which were inter-regional features. The turning-point of the developmental trajectories in human brain was around 40 years old based on regional cortical thickness. In conclusion, structural MRI could be potential biomarkers for the aging in human brain. The human age could be successfully predicted from the combination of regional morphometry and inter-regional morphological similarity. The inter-regional measures could be beneficial to investigating human brain connectome.

  6. Progression of Multiple Behavioral Deficits with Various Age of Onset in a Murine Model of Hurler Syndrome

    PubMed Central

    Pan, Dao; Sciascia, Anthony; Vorhees, Charles V.; Williams, Michael T.

    2008-01-01

    Mucopolysaccharidosis type I (MPS I) is one of the most common lysosomal storage diseases with progressive neurological dysfunction. To characterize the chronological behavioral profiles and identify the onset of functional deficits in a MPS I mouse model (IDUA−/−), we evaluated anxiety, locomotor behavior, startle, spatial learning and memory with mice at 2-, 4-, 6- and 8- months of age. In automated open-field test, IDUA−/− mice showed hypoactivity as early as 2- months of age and altered anxiety starting from 6-months of age during the initial exploratory phase, even through normal habituation was observed at all ages. In the marble-burying task, the anxiety-like compulsive behavior was normal in IDUA−/− mice at almost all tested ages, but significantly reduced in 8-month old male IDUA−/− mice which coincided with the rapid death of IDUA−/− males starting from 7-months of age. In the Morris water maze, IDUA−/− mice exhibited impaired proficient learning only at 4-months of age during the acquisition phase. Spatial memory deficits were observed in IDUA−/− mice during both 1- and 7-days probe trials at 4- and 8-months of age. The IDUA−/− mice performed normally in a novel object recognition task at younger ages until 8 month old when reduced visual cognitive memory retention was noted in the IDUA−/− mice. In addition, 8-month old IDUA−/− mice failed to habituate to repeated open-field exposure, suggesting deficits in nonaversive and non-associative memory. In acoustic startle assessment, significantly more non-responders were found in IDUA−/−, but normal performance was seen in those that did show a response. These results presented a temporal evaluation of phenotypic behavioral dysfunctions in IDUA−/− mice from adolescent to maturity, indicating the impairments, with different age of onset, in locomotor and anxiety-like compulsive behaviors, spatial learning and memory, visual recognition, and short-term non

  7. Human computers: the first pioneers of the information age.

    PubMed

    Grier, D A

    2001-03-01

    Before computers were machines, they were people. They were men and women, young and old, well educated and common. They were the workers who convinced scientists that large-scale calculation had value. Long before Presper Eckert and John Mauchly built the ENIAC at the Moore School of Electronics, Philadelphia, or Maurice Wilkes designed the EDSAC for Manchester University, human computers had created the discipline of computation. They developed numerical methodologies and proved them on practical problems. These human computers were not savants or calculating geniuses. Some knew little more than basic arithmetic. A few were near equals of the scientists they served and, in a different time or place, might have become practicing scientists had they not been barred from a scientific career by their class, education, gender or ethnicity.

  8. DNA technological progress toward advanced diagnostic tools to support human hookworm control.

    PubMed

    Gasser, R B; Cantacessi, C; Loukas, A

    2008-01-01

    Blood-feeding hookworms are parasitic nematodes of major human health importance. Currently, it is estimated that 740 million people are infected worldwide, and more than 80 million of them are severely affected clinically by hookworm disease. In spite of the health problems caused and the advances toward the development of vaccines against some hookworms, limited attention has been paid to the need for improved, practical methods of diagnosis. Accurate diagnosis and genetic characterization of hookworms is central to their effective control. While traditional diagnostic methods have considerable limitations, there has been some progress toward the development of molecular-diagnostic tools. The present article provides a brief background on hookworm disease of humans, reviews the main methods that have been used for diagnosis and describes progress in establishing polymerase chain reaction (PCR)-based methods for the specific diagnosis of hookworm infection and the genetic characterisation of the causative agents. This progress provides a foundation for the rapid development of practical, highly sensitive and specific diagnostic and analytical tools to be used in improved hookworm prevention and control programmes.

  9. Biological and Clinicopathological Significance of Cripto-1 Expression in the Progression of Human ESCC

    PubMed Central

    Mahmoudian, Reihaneh Alsadat; Abbaszadegan, Mohammad Reza; Forghanifard, Mohammad Mahdi; Moghbeli, Meysam; Moghbeli, Faezeh; Chamani, Jamshidkhan; Gholamin, Mehran

    2017-01-01

    Background: Human Cripto-1, a member of the EGF-CFC family, is involved in embryonic development, embryonic stem cell maintenance, and tumor progression. It also participates in multiple cell signaling pathways including Wnt, Notch, and TGF-β. Remarkably, it is expressed in cancer stem cell (CSC) compartments, boosting tumor cell migration, invasion, and angiogenesis. Although Cripto-1 is overexpressed in a variety of human malignant tumors, its expression in esophageal squamous cell carcinoma (ESCC) remains unclear. Our aim in this study was to evaluate the possible oncogenic role of Cripto-1 in ESCC progression and elucidate its association with clinicopathological parameters in patients. Methods: In this study, Cripto-1 expression in 50 ESCC tissue samples was analyzed and compared to corresponding margin-normal esophageal tissues using quantitative real-time PCR. Results: Cripto-1 was overexpressed in nearly 40% of ESCC samples compared with normal tissue samples. Significant correlations were observed between Cripto-1 expression and tumor differentiation grade, progression stage, and location (p < 0.05). Conclusions: Our results indicate that overexpression of Cripto-1 is involved in the development of ESCC. Further assessment will be necessary to determine the role of Cripto-1 cross talk in ESCC tumorigenesis. PMID:28367468

  10. Cell type-dependent pathogenic functions of overexpressed human cathepsin B in murine breast cancer progression

    PubMed Central

    Bengsch, F; Buck, A; Günther, SC; Seiz, JR; Tacke, M; Pfeifer, D; von Elverfeldt, D; Sevenich, L; Hillebrand, LE; Kern, U; Sameni, M; Peters, C; Sloane, BF; Reinheckel, T

    2014-01-01

    The cysteine protease cathepsin B (CTSB) is frequently overexpressed in human breast cancer and correlated with a poor prognosis. Genetic deficiency or pharmacological inhibition of CTSB attenuates tumor growth, invasion and metastasis in mouse models of human cancers. CTSB is expressed in both cancer cells and cells of the tumor stroma, in particular in tumor-associated macrophages (TAM). In order to evaluate the impact of tumor- or stromal cell-derived CTSB on Polyoma Middle T (PyMT)-induced breast cancer progression, we used in vivo and in vitro approaches to induce human CTSB overexpression in PyMT cancer cells or stromal cells alone or in combination. Orthotopic transplantation experiments revealed that CTSB overexpression in cancer cells rather than in the stroma affects PyMT tumor progression. In 3D cultures, primary PyMT tumor cells showed higher extracellular matrix proteolysis and enhanced collective cell invasion when CTSB was overexpressed and proteolytically active. Coculture of PyMT cells with bone marrow-derived macrophages induced a TAM-like macrophage phenotype in vitro, and the presence of such M2-polarized macrophages in 3D cultures enhanced sprouting of tumor spheroids. We employed a doxycycline (DOX)-inducible CTSB expression system to selectively overexpress human CTSB either in cancer cells or in macrophages in 3D cocultures. Tumor spheroid invasiveness was only enhanced when CTSB was overexpressed in cancer cells, whereas CTSB expression in macrophages alone did not further promote invasiveness of tumor spheroids. We conclude that CTSB overexpression in the PyMT mouse model promotes tumor progression not by a stromal effect, but by a direct, cancer cell-inherent mode of action: CTSB overexpression renders the PyMT cancers more invasive by increasing proteolytic extracellular matrix protein degradation fostering collective cell invasion into adjacent tissue. PMID:24077280

  11. The adaptive endoplasmic reticulum stress response to lipotoxicity in progressive human nonalcoholic fatty liver disease.

    PubMed

    Lake, April D; Novak, Petr; Hardwick, Rhiannon N; Flores-Keown, Brieanna; Zhao, Fei; Klimecki, Walter T; Cherrington, Nathan J

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) may progress from simple steatosis to severe, nonalcoholic steatohepatitis (NASH) in 7%-14% of the U.S. population through a second "hit" in the form of increased oxidative stress and inflammation. Endoplasmic reticulum (ER) stress signaling and the unfolded protein response (UPR) are triggered when high levels of lipids and misfolded proteins alter ER homeostasis creating a lipotoxic environment within NAFLD livers. The objective of this study was to determine the coordinate regulation of ER stress-associated genes in the progressive stages of human NAFLD. Human liver samples categorized as normal, steatosis, NASH (Fatty), and NASH (Not Fatty) were analyzed by individual Affymetrix GeneChip Human 1.0 ST microarrays, immunoblots, and immunohistochemistry. A gene set enrichment analysis was performed on autophagy, apoptosis, lipogenesis, and ER stress/UPR gene categories. An enrichment of downregulated genes in the ER stress-associated lipogenesis and ER stress/UPR gene categories was observed in NASH. Conversely, an enrichment of upregulated ER stress-associated genes for autophagy and apoptosis gene categories was observed in NASH. Protein expression of the adaptive liver response protein STC2 and the transcription factor X-box binding protein 1 spliced (XBP-1s) were significantly elevated among NASH samples, whereas other downstream ER stress proteins including CHOP, ATF4, and phosphorylated JNK and eIF2α were not significantly changed in disease progression. Increased nuclear accumulation of total XBP-1 protein was observed in steatosis and NASH livers. The findings reveal the presence of a coordinated, adaptive transcriptional response to hepatic ER stress in human NAFLD.

  12. Functional Changes in the Human Auditory Cortex in Ageing

    PubMed Central

    Profant, Oliver; Tintěra, Jaroslav; Balogová, Zuzana; Ibrahim, Ibrahim; Jilek, Milan; Syka, Josef

    2015-01-01

    Hearing loss, presbycusis, is one of the most common sensory declines in the ageing population. Presbycusis is characterised by a deterioration in the processing of temporal sound features as well as a decline in speech perception, thus indicating a possible central component. With the aim to explore the central component of presbycusis, we studied the function of the auditory cortex by functional MRI in two groups of elderly subjects (>65 years) and compared the results with young subjects (age-related changes at the level of the auditory cortex. The fMRI showed only minimal activation in response to the 8 kHz stimulation, despite the fact that all subjects heard the stimulus. Both elderly groups showed greater activation in response to acoustical stimuli in the temporal lobes in comparison with young subjects. In addition, activation in the right temporal lobe was more expressed than in the left temporal lobe in both elderly groups, whereas in the young control subjects (YC) leftward lateralization was present. No statistically significant differences in activation of the auditory cortex were found between the MP and EP groups. The greater extent of cortical activation in elderly subjects in comparison with young subjects, with an asymmetry towards the right side, may serve as a compensatory mechanism for the impaired processing of auditory information appearing as a consequence of ageing. PMID:25734519

  13. Functional changes in the human auditory cortex in ageing.

    PubMed

    Profant, Oliver; Tintěra, Jaroslav; Balogová, Zuzana; Ibrahim, Ibrahim; Jilek, Milan; Syka, Josef

    2015-01-01

    Hearing loss, presbycusis, is one of the most common sensory declines in the ageing population. Presbycusis is characterised by a deterioration in the processing of temporal sound features as well as a decline in speech perception, thus indicating a possible central component. With the aim to explore the central component of presbycusis, we studied the function of the auditory cortex by functional MRI in two groups of elderly subjects (>65 years) and compared the results with young subjects (age-related changes at the level of the auditory cortex. The fMRI showed only minimal activation in response to the 8 kHz stimulation, despite the fact that all subjects heard the stimulus. Both elderly groups showed greater activation in response to acoustical stimuli in the temporal lobes in comparison with young subjects. In addition, activation in the right temporal lobe was more expressed than in the left temporal lobe in both elderly groups, whereas in the young control subjects (YC) leftward lateralization was present. No statistically significant differences in activation of the auditory cortex were found between the MP and EP groups. The greater extent of cortical activation in elderly subjects in comparison with young subjects, with an asymmetry towards the right side, may serve as a compensatory mechanism for the impaired processing of auditory information appearing as a consequence of ageing.

  14. Clinical and genetic factors associated with progression of geographic atrophy lesions in age-related macular degeneration.

    PubMed

    Grassmann, Felix; Fleckenstein, Monika; Chew, Emily Y; Strunz, Tobias; Schmitz-Valckenberg, Steffen; Göbel, Arno P; Klein, Michael L; Ratnapriya, Rinki; Swaroop, Anand; Holz, Frank G; Weber, Bernhard H F

    2015-01-01

    Worldwide, age-related macular degeneration (AMD) is a serious threat to vision loss in individuals over 50 years of age with a pooled prevalence of approximately 9%. For 2020, the number of people afflicted with this condition is estimated to reach 200 million. While AMD lesions presenting as geographic atrophy (GA) show high inter-individual variability, only little is known about prognostic factors. Here, we aimed to elucidate the contribution of clinical, demographic and genetic factors on GA progression. Analyzing the currently largest dataset on GA lesion growth (N = 388), our findings suggest a significant and independent contribution of three factors on GA lesion growth including at least two genetic factors (ARMS2_rs10490924 [P < 0.00088] and C3_rs2230199 [P < 0.00015]) as well as one clinical component (presence of GA in the fellow eye [P < 0.00023]). These correlations jointly explain up to 7.2% of the observed inter-individual variance in GA lesion progression and should be considered in strategy planning of interventional clinical trials aimed at evaluating novel treatment options in advanced GA due to AMD.

  15. Privacy and human behavior in the age of information.

    PubMed

    Acquisti, Alessandro; Brandimarte, Laura; Loewenstein, George

    2015-01-30

    This Review summarizes and draws connections between diverse streams of empirical research on privacy behavior. We use three themes to connect insights from social and behavioral sciences: people's uncertainty about the consequences of privacy-related behaviors and their own preferences over those consequences; the context-dependence of people's concern, or lack thereof, about privacy; and the degree to which privacy concerns are malleable—manipulable by commercial and governmental interests. Organizing our discussion by these themes, we offer observations concerning the role of public policy in the protection of privacy in the information age.

  16. Sex-specific differences in age-dependent progression of aortic dysfunction and related cardiac remodeling in spontaneously hypertensive rats.

    PubMed

    Al-Gburi, Suzan; Deussen, Andreas Johannes; Galli, Roberta; Muders, Michael H; Zatschler, Birgit; Neisser, Anja; Müller, Bianca; Kopaliani, Irakli

    2017-03-08

    Sex-specific differences in renin-angiotensin-system (RAS) and arterial pressure have been evidenced in many mammals including spontaneously hypertensive rats (SHRs). Although SHRs have been used extensively as a leading experimental model of hypertension, effects of sex-specific differences in RAS on aortic function and related cardiac remodeling during aging and hypertension have not been documented in detail. We examined structural and functional changes in aorta and heart of female and male SHRs at ages of 5, 14, 29 and 36-weeks. SHRs of both sexes were hypertensive from 14-weeks. Aortic endothelial dysfunction and fibrosis, left ventricular (LV) hypertrophy and cardiac fibrosis was evident at the age of 29-weeks in male SHRs, but first appeared only at the age of 36-weeks in female SHRs. There was a pronounced delay of matrix metalloproteinase-2 activity in aorta and heart of female SHRs, which was associated with preservation of 40 % more elastin and less extensive cardiac fibrosis than in males. At 5, 29 and 36-weeks of age female SHRs showed higher levels of aortic and myocardial AT2R and MasR mRNA and decreased ANGII-mediated aortic constriction. While female SHRs had increased relaxation to AT2R stimulation at 5 and 29-weeks compared to males, this difference disappeared at 36-weeks of age. This study documents sex-specific differences in the temporal progression of aortic dysfunction and LV hypertrophy in SHRs which are independent of arterial pressure and are apparently mediated by higher AT2R expression in the heart and aorta of female SHRs.

  17. How the effects of aging and stresses of life are integrated in mortality rates: insights for genetic studies of human health and longevity.

    PubMed

    Yashin, Anatoliy I; Arbeev, Konstantin G; Arbeeva, Liubov S; Wu, Deqing; Akushevich, Igor; Kovtun, Mikhail; Yashkin, Arseniy; Kulminski, Alexander; Culminskaya, Irina; Stallard, Eric; Li, Miaozhu; Ukraintseva, Svetlana V

    2016-02-01

    Increasing proportions of elderly individuals in developed countries combined with substantial increases in related medical expenditures make the improvement of the health of the elderly a high priority today. If the process of aging by individuals is a major cause of age related health declines then postponing aging could be an efficient strategy for improving the health of the elderly. Implementing this strategy requires a better understanding of genetic and non-genetic connections among aging, health, and longevity. We review progress and problems in research areas whose development may contribute to analyses of such connections. These include genetic studies of human aging and longevity, the heterogeneity of populations with respect to their susceptibility to disease and death, forces that shape age patterns of human mortality, secular trends in mortality decline, and integrative mortality modeling using longitudinal data. The dynamic involvement of genetic factors in (i) morbidity/mortality risks, (ii) responses to stresses of life, (iii) multi-morbidities of many elderly individuals, (iv) trade-offs for diseases, (v) genetic heterogeneity, and (vi) other relevant aging-related health declines, underscores the need for a comprehensive, integrated approach to analyze the genetic connections for all of the above aspects of aging-related changes. The dynamic relationships among aging, health, and longevity traits would be better understood if one linked several research fields within one conceptual framework that allowed for efficient analyses of available longitudinal data using the wealth of available knowledge about aging, health, and longevity already accumulated in the research field.

  18. Aging and Surveillance Program MINUTEMAN II/III Stage II Program Progress.

    DTIC Science & Technology

    1985-11-01

    130 Firing Adapters Used to Fire VECP Igniters 58 132 Squib Arrangement Used in Both KR80000 Safe and Arm and FFTFs 59 133 Bladder Permeation vs Age...hydrolytic liner degradation as the primary mechanism leading ; . " to failure for the motor. Kinetic projections for service life ranged from 14 to 17...the igniter following assembly . In general, propellant in the bulk of the web is slightly harder than that measured in the fin. Propellant in the slot

  19. AGE-RELATED GENE EXPRESSION CHANGES IN HUMAN SKIN FIBROBLASTS INDUCED BY MMS

    EPA Science Inventory

    Age-Related Gene Expression Changes In Human Skin Fibroblasts Induced By methyl methanesulfonate. Geremy W. Knapp, Alan H. Tennant, and Russell D. Owen. Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory, U. S. Environmental Prote...

  20. A decline in PABPN1 induces progressive muscle weakness in oculopharyngeal muscle dystrophy and in muscle aging.

    PubMed

    Anvar, Seyed Yahya; Raz, Yotam; Verway, Nisha; van der Sluijs, Barbara; Venema, Andrea; Goeman, Jelle J; Vissing, John; van der Maarel, Silvère M; 't Hoen, Peter A C; van Engelen, Baziel G M; Raz, Vered

    2013-06-01

    Oculopharyngeal muscular dystrophy (OPMD) is caused by trinucleotide repeat expansion mutations in Poly(A) binding protein 1 (PABPN1). PABPN1 is a regulator of mRNA stability and is ubiquitously expressed. Here we investigated how symptoms in OPMD initiate only at midlife and why a subset of skeletal muscles is predominantly affected. Genome-wide RNA expression profiles from Vastus lateralis muscles human carriers of expanded-PABPN1 at pre-symptomatic and symptomatic stages were compared with healthy controls. Major expression changes were found to be associated with age rather than with expression of expanded-PABPN1, instead transcriptomes of OPMD and elderly muscles were significantly similar (P<0.05). Using k-means clustering we identified age-dependent trends in both OPMD and controls, but trends were often accelerated in OPMD. We report an age-regulated decline in PABPN1 levels in Vastus lateralis muscles from the fifth decade. In concurrence with severe muscle degeneration in OPMD, the decline in PABPN1 accelerated in OPMD and was specific to skeletal muscles. Reduced PABPN1 levels (30% to 60%) in muscle cells induced myogenic defects and morphological signatures of cellular aging in proportion to PABPN1 expression levels. We suggest that PABPN1 levels regulate muscle cell aging and OPMD represents an accelerated muscle aging disorder.

  1. Aging causes morphological alterations in astrocytes and microglia in human substantia nigra pars compacta.

    PubMed

    Jyothi, H J; Vidyadhara, D J; Mahadevan, Anita; Philip, Mariamma; Parmar, Suresh Kumar; Manohari, S Gowri; Shankar, S K; Raju, Trichur R; Alladi, Phalguni Anand

    2015-12-01

    Age being a risk factor for Parkinson's disease, assessment of age-related changes in the human substantia nigra may elucidate its pathogenesis. Increase in Marinesco bodies, α-synuclein, free radicals and so forth in the aging nigral neurons are clear indicators of neurodegeneration. Here, we report the glial responses in aging human nigra. The glial numbers were determined on Nissl-stained sections. The expression of glial fibrillary acidic protein, S100β, 2', 3'-cyclic nucleotide 3' phosphodiesterase, and Iba1 was assessed on cryosections of autopsied midbrains by immunohistochemistry and densitometry. The glial counts showed a biphasic increase, of which, the first prominent phase from fetal age to birth could be physiological gliogenesis whereas the second one after middle age may reflect mild age-related gliosis. Astrocytic morphology was altered, but glial fibrillary acidic protein expression increased only mildly. Presence of type-4 microglia suggests possibility of neuroinflammation. Mild reduction in 2', 3'-cyclic nucleotide 3' phosphodiesterase-labeled area denotes subtle demyelination. Stable age-related S100β expression indicates absence of calcium overload. Against the expected prominent gliosis, subtle age-related morphological alterations in human nigral glia attribute them a participatory role in aging.

  2. Serum Levels of Toxic AGEs (TAGE) May Be a Promising Novel Biomarker for the Onset/Progression of Lifestyle-Related Diseases

    PubMed Central

    Takeuchi, Masayoshi

    2016-01-01

    Advanced glycation end-products (AGEs) generated with aging or in the presence of diabetes mellitus, particularly AGEs derived from the glucose/fructose metabolism intermediate glyceraldehyde (Glycer-AGEs; termed toxic AGEs (TAGE)), were recently shown to be closely involved in the onset/progression of diabetic vascular complications via the receptor for AGEs (RAGE). TAGE also contribute to various diseases, such as cardiovascular disease; nonalcoholic steatohepatitis; cancer; Alzheimer’s disease, and; infertility. This suggests the necessity of minimizing the influence of the TAGE-RAGE axis in order to prevent the onset/progression of lifestyle-related diseases (LSRD) and establish therapeutic strategies. Changes in serum TAGE levels are closely associated with LSRD related to overeating, a lack of exercise, or excessive ingestion of sugars/dietary AGEs. We also showed that serum TAGE levels, but not those of hemoglobin A1c, glucose-derived AGEs, or Nε-(carboxymethyl)lysine, have potential as a biomarker for predicting the progression of atherosclerosis and future cardiovascular events. We herein introduce the usefulness of serum TAGE levels as a biomarker for the prevention/early diagnosis of LSRD and the evaluation of the efficacy of treatments; we discuss whether dietary AGE/sugar intake restrictions reduce the generation/accumulation of TAGE, thereby preventing the onset/progression of LSRD. PMID:27338481

  3. Emerging of fractal geometry on surface of human cervical epithelial cells during progression towards cancer.

    PubMed

    Dokukin, M E; Guz, N V; Woodworth, C D; Sokolov, I

    2015-03-10

    Despite considerable advances in understanding the molecular nature of cancer, many biophysical aspects of malignant development are still unclear. Here we study physical alterations of the surface of human cervical epithelial cells during stepwise in vitro development of cancer (from normal to immortal (premalignant), to malignant). We use atomic force microscopy to demonstrate that development of cancer is associated with emergence of simple fractal geometry on the cell surface. Contrary to the previously expected correlation between cancer and fractals, we find that fractal geometry occurs only at a limited period of development when immortal cells become cancerous; further cancer progression demonstrates deviation from fractal. Because of the connection between fractal behaviour and chaos (or far from equilibrium behaviour), these results suggest that chaotic behaviour coincides with the cancer transformation of the immortalization stage of cancer development, whereas further cancer progression recovers determinism of processes responsible for cell surface formation.

  4. Emergence of fractal geometry on the surface of human cervical epithelial cells during progression towards cancer

    NASA Astrophysics Data System (ADS)

    Dokukin, M. E.; Guz, N. V.; Woodworth, C. D.; Sokolov, I.

    2015-03-01

    Despite considerable advances in understanding the molecular nature of cancer, many biophysical aspects of malignant development are still unclear. Here we study physical alterations of the surface of human cervical epithelial cells during stepwise in vitro development of cancer (from normal to immortal (premalignant), to malignant). We use atomic force microscopy to demonstrate that development of cancer is associated with emergence of simple fractal geometry on the cell surface. Contrary to the previously expected correlation between cancer and fractals, we find that fractal geometry occurs only at a limited period of development when immortal cells become cancerous; further cancer progression demonstrates deviation from fractal. Because of the connection between fractal behaviour and chaos (or far from equilibrium behaviour), these results suggest that chaotic behaviour coincides with the cancer transformation of the immortalization stage of cancer development, whereas further cancer progression recovers determinism of processes responsible for cell surface formation.

  5. Effects of Age on Na+,K+-ATPase Expression in Human and Rodent Skeletal Muscle

    PubMed Central

    Wyckelsma, Victoria L.; McKenna, Michael J.

    2016-01-01

    The maintenance of transmembrane Na+ and K+ concentration gradients and membrane potential is vital for the production of force in skeletal muscle. In aging an inability to maintain ion regulation and membrane potential would have adverse consequences on the capacity for performing repeated muscle contractions, which are critical for everyday activities and functional independence. This short review focusses on the effects of aging on one major and vital component affecting muscle Na+ and K+ concentrations, membrane potential and excitability in skeletal muscle, the Na+,K+-ATPase (Na+,K+-pump, NKA) protein. The review examines the effects of age on NKA in both human and rodent models and highlights a distant lack of research in NKA with aging. In rodents, the muscle NKA measured by [3H]ouabain binding site content, declines with advanced age from peak values in early life. In human skeletal muscle, however, there appears to be no age effect on [3H]ouabain binding site content in physically active older adults between 55 and 76 years compared to those aged between 18 and 30 years of age. Analysis of the NKA isoforms reveal differential changes with age in fiber-types in both rat and humans. The data show considerable disparities, suggesting different regulation of NKA isoforms between rodents and humans. Finally we review the importance of physical activity on NKA content in older humans. Findings suggest that physical activity levels of an individual may have a greater effect on regulating the NKA content in skeletal muscle rather than aging per se, at least up until 80 years of age. PMID:27531982

  6. Aging and Replicative Senescence Have Related Effects on Human Stem and Progenitor Cells

    PubMed Central

    Wagner, Wolfgang; Bork, Simone; Horn, Patrick; Krunic, Damir; Walenda, Thomas; Diehlmann, Anke; Benes, Vladimir; Blake, Jonathon; Huber, Franz-Xaver; Eckstein, Volker; Boukamp, Petra; Ho, Anthony D.

    2009-01-01

    The regenerative potential diminishes with age and this has been ascribed to functional impairments of adult stem cells. Cells in culture undergo senescence after a certain number of cell divisions whereby the cells enlarge and finally stop proliferation. This observation of replicative senescence has been extrapolated to somatic stem cells in vivo and might reflect the aging process of the whole organism. In this study we have analyzed the effect of aging on gene expression profiles of human mesenchymal stromal cells (MSC) and human hematopoietic progenitor cells (HPC). MSC were isolated from bone marrow of donors between 21 and 92 years old. 67 genes were age-induced and 60 were age-repressed. HPC were isolated from cord blood or from mobilized peripheral blood of donors between 27 and 73 years and 432 genes were age-induced and 495 were age-repressed. The overlap of age-associated differential gene expression in HPC and MSC was moderate. However, it was striking that several age-related gene expression changes in both MSC and HPC were also differentially expressed upon replicative senescence of MSC in vitro. Especially genes involved in genomic integrity and regulation of transcription were age-repressed. Although telomerase activity and telomere length varied in HPC particularly from older donors, an age-dependent decline was not significant arguing against telomere exhaustion as being causal for the aging phenotype. These studies have demonstrated that aging causes gene expression changes in human MSC and HPC that vary between the two different cell types. Changes upon aging of MSC and HPC are related to those of replicative senescence of MSC in vitro and this indicates that our stem and progenitor cells undergo a similar process also in vivo. PMID:19513108

  7. Aging and replicative senescence have related effects on human stem and progenitor cells.

    PubMed

    Wagner, Wolfgang; Bork, Simone; Horn, Patrick; Krunic, Damir; Walenda, Thomas; Diehlmann, Anke; Benes, Vladimir; Blake, Jonathon; Huber, Franz-Xaver; Eckstein, Volker; Boukamp, Petra; Ho, Anthony D

    2009-06-09

    The regenerative potential diminishes with age and this has been ascribed to functional impairments of adult stem cells. Cells in culture undergo senescence after a certain number of cell divisions whereby the cells enlarge and finally stop proliferation. This observation of replicative senescence has been extrapolated to somatic stem cells in vivo and might reflect the aging process of the whole organism. In this study we have analyzed the effect of aging on gene expression profiles of human mesenchymal stromal cells (MSC) and human hematopoietic progenitor cells (HPC). MSC were isolated from bone marrow of donors between 21 and 92 years old. 67 genes were age-induced and 60 were age-repressed. HPC were isolated from cord blood or from mobilized peripheral blood of donors between 27 and 73 years and 432 genes were age-induced and 495 were age-repressed. The overlap of age-associated differential gene expression in HPC and MSC was moderate. However, it was striking that several age-related gene expression changes in both MSC and HPC were also differentially expressed upon replicative senescence of MSC in vitro. Especially genes involved in genomic integrity and regulation of transcription were age-repressed. Although telomerase activity and telomere length varied in HPC particularly from older donors, an age-dependent decline was not significant arguing against telomere exhaustion as being causal for the aging phenotype. These studies have demonstrated that aging causes gene expression changes in human MSC and HPC that vary between the two different cell types. Changes upon aging of MSC and HPC are related to those of replicative senescence of MSC in vitro and this indicates that our stem and progenitor cells undergo a similar process also in vivo.

  8. Palaeopathology of human remains from the Roman Imperial Age.

    PubMed

    Minozzi, Simona; Catalano, Paola; Caldarini, Carla; Fornaciari, Gino

    2012-01-01

    The increasing attention of archaeological and anthropological research towards palaeopathological studies has allowed to focus the examination of many skeletal samples on this aspect and to evaluate the presence of many diseases afflicting ancient populations. This paper describes the most interesting diseases observed in skeletal samples from five necropolises found in urban and suburban areas of Rome during archaeological excavations in the last decades, and dating back to the Imperial Age. The diseases observed were grouped into the following categories: articular diseases, traumas, infections, metabolic or nutritional diseases, congenital diseases and tumors, and some examples are reported for each group. Although extensive epidemiological investigation in ancient skeletal records is impossible, palaeopathology allowed highlighting the spread of numerous illnesses, many of which can be related to the life and health conditions of the Roman population.

  9. Deep biomarkers of human aging: Application of deep neural networks to biomarker development

    PubMed Central

    Putin, Evgeny; Mamoshina, Polina; Aliper, Alexander; Korzinkin, Mikhail; Moskalev, Alexey; Kolosov, Alexey; Ostrovskiy, Alexander; Cantor, Charles; Vijg, Jan; Zhavoronkov, Alex

    2016-01-01

    One of the major impediments in human aging research is the absence of a comprehensive and actionable set of biomarkers that may be targeted and measured to track the effectiveness of therapeutic interventions. In this study, we designed a modular ensemble of 21 deep neural networks (DNNs) of varying depth, structure and optimization to predict human chronological age using a basic blood test. To train the DNNs, we used over 60,000 samples from common blood biochemistry and cell count tests from routine health exams performed by a single laboratory and linked to chronological age and sex. The best performing DNN in the ensemble demonstrated 81.5 % epsilon-accuracy r = 0.90 with R2 = 0.80 and MAE = 6.07 years in predicting chronological age within a 10 year frame, while the entire ensemble achieved 83.5% epsilon-accuracy r = 0.91 with R2 = 0.82 and MAE = 5.55 years. The ensemble also identified the 5 most important markers for predicting human chronological age: albumin, glucose, alkaline phosphatase, urea and erythrocytes. To allow for public testing and evaluate real-life performance of the predictor, we developed an online system available at http://www.aging.ai. The ensemble approach may facilitate integration of multi-modal data linked to chronological age and sex that may lead to simple, minimally invasive, and affordable methods of tracking integrated biomarkers of aging in humans and performing cross-species feature importance analysis. PMID:27191382

  10. Deep biomarkers of human aging: Application of deep neural networks to biomarker development.

    PubMed

    Putin, Evgeny; Mamoshina, Polina; Aliper, Alexander; Korzinkin, Mikhail; Moskalev, Alexey; Kolosov, Alexey; Ostrovskiy, Alexander; Cantor, Charles; Vijg, Jan; Zhavoronkov, Alex

    2016-05-01

    One of the major impediments in human aging research is the absence of a comprehensive and actionable set of biomarkers that may be targeted and measured to track the effectiveness of therapeutic interventions. In this study, we designed a modular ensemble of 21 deep neural networks (DNNs) of varying depth, structure and optimization to predict human chronological age using a basic blood test. To train the DNNs, we used over 60,000 samples from common blood biochemistry and cell count tests from routine health exams performed by a single laboratory and linked to chronological age and sex. The best performing DNN in the ensemble demonstrated 81.5 % epsilon-accuracy r = 0.90 with R(2) = 0.80 and MAE = 6.07 years in predicting chronological age within a 10 year frame, while the entire ensemble achieved 83.5% epsilon-accuracy r = 0.91 with R(2) = 0.82 and MAE = 5.55 years. The ensemble also identified the 5 most important markers for predicting human chronological age: albumin, glucose, alkaline phosphatase, urea and erythrocytes. To allow for public testing and evaluate real-life performance of the predictor, we developed an online system available at http://www.aging.ai. The ensemble approach may facilitate integration of multi-modal data linked to chronological age and sex that may lead to simple, minimally invasive, and affordable methods of tracking integrated biomarkers of aging in humans and performing cross-species feature importance analysis.

  11. On the Increasing Fragility of Human Teeth with Age: ADeep-Ultraviolet Resonance Raman Study

    SciTech Connect

    Ager III, J.W.; Nalla, R.K.; Balooch, G.; Kim, G.; Pugach, M.; Habelitz, S.; Marshall, G.W.; Kinney, J.H.; Ritchie, R.O.

    2006-07-14

    Ultraviolet resonance Raman spectroscopy (UVRRS) using 244nm excitation was used to investigate the impact of aging on humandentin. The intensity of a spectroscopic feature from the peptide bondsin the collagen increases with tissue age, similar to a finding reportedpreviously for human cortical bone.

  12. Age-Dependent Oxidative DNA Damage Does Not Correlate with Reduced Proliferation of Cardiomyocytes in Humans

    PubMed Central

    Li, Minghui; Liu, Jinfen; Jiang, Chuan; Zhang, Haibo; Ye, Lincai; Zheng, Jinghao

    2017-01-01

    Background Postnatal human cardiomyocyte proliferation declines rapidly with age, which has been suggested to be correlated with increases in oxidative DNA damage in mice and plays an important role in regulating cardiomyocyte proliferation. However, the relationship between oxidative DNA damage and age in humans is unclear. Methods Sixty right ventricular outflow myocardial tissue specimens were obtained from ventricular septal defect infant patients during routine congenital cardiac surgery. These specimens were divided into three groups based on age: group A (age 0–6 months), group B (age, 7–12 months), and group C (>12 months). Each tissue specimen was subjected to DNA extraction, RNA extraction, and immunofluorescence. Results Immunofluorescence and qRT-PCR analysis revealed that DNA damage markers—mitochondrial DNA copy number, oxoguanine 8, and phosphorylated ataxia telangiectasia mutated—were highest in Group B. However immunofluorescence and qRT-PCR demonstrated that two cell proliferation markers, Ki67 and cyclin D2, were decreased with age. In addition, wheat germ agglutinin-staining indicated that the average size of cardiomyocytes increased with age. Conclusions Oxidative DNA damage of cardiomyocytes was not correlated positively with age in human beings. Oxidative DNA damage is unable to fully explain the reduced proliferation of human cardiomyocytes. PMID:28099512

  13. Ontogeny and aging of the distal skin temperature rhythm in humans.

    PubMed

    Batinga, H; Martinez-Nicolas, A; Zornoza-Moreno, M; Sánchez-Solis, M; Larqué, E; Mondéjar, M T; Moreno-Casbas, M; García, F J; Campos, M; Rol, M A; Madrid, J A

    2015-01-01

    In circadian terms, human ontogeny is characterized by the emergence of a daily pattern, from a previous ultradian pattern, for most variables during the first 6 months of life. Circadian aging in humans is characterized by a phase advance, accompanied by rhythm fragmentation and flattening. Despite an expanding body of literature focused on distal skin temperature, little information is available about the ontogeny and practically nothing about age-related changes in this rhythm. Thus, the aim was to evaluate the degree of maturation and aging of the circadian pattern of distal skin temperature to identify those parameters that are modified throughout life and could be used to differentiate subjects according to their age. For this, distal skin temperature was measured in 197 volunteers (55 % women), including babies aged 15 days (30 subjects), 1 month (28 subjects), 3 months (31 subjects), and 6 months (10 subjects); young adults aged 19 years (37 subjects); middle-aged persons aged 46 years (27 subjects); older people aged 72 (34 subjects). Circadian system maturation was associated with an increase in amplitude and a reduction in skin temperature during sleep. During adulthood, women showed a more robust pattern (lower fragmentation, and higher night-time temperature, amplitude, circadian function index, and first harmonic relative power); however, these differences were lost with aging, a period of life that was consistently associated with a phase advance of the rhythm. In summary, distal skin temperature pattern can be used as a robust variable to discern between different ages throughout the life.

  14. Metrics for the Human Proteome Project 2015: Progress on the Human Proteome and Guidelines for High-Confidence Protein Identification.

    PubMed

    Omenn, Gilbert S; Lane, Lydie; Lundberg, Emma K; Beavis, Ronald C; Nesvizhskii, Alexey I; Deutsch, Eric W

    2015-09-04

    Remarkable progress continues on the annotation of the proteins identified in the Human Proteome and on finding credible proteomic evidence for the expression of "missing proteins". Missing proteins are those with no previous protein-level evidence or insufficient evidence to make a confident identification upon reanalysis in PeptideAtlas and curation in neXtProt. Enhanced with several major new data sets published in 2014, the human proteome presented as neXtProt, version 2014-09-19, has 16,491 unique confident proteins (PE level 1), up from 13,664 at 2012-12 and 15,646 at 2013-09. That leaves 2948 missing proteins from genes classified having protein existence level PE 2, 3, or 4, as well as 616 dubious proteins at PE 5. Here, we document the progress of the HPP and discuss the importance of assessing the quality of evidence, confirming automated findings and considering alternative protein matches for spectra and peptides. We provide guidelines for proteomics investigators to apply in reporting newly identified proteins.

  15. Development and Aging of the Healthy Human Brain Uncinate Fasciculus across the Lifespan using Diffusion Tensor Tractography

    PubMed Central

    Hasan, Khader M.; Iftikhar, Amal; Kamali, Arash; Kramer, Larry A.; Ashtari, Manzar; Cirino, Paul T.; Papanicolaou, Andrew C.; Fletcher, Jack M.; Ewing-Cobbs, Linda

    2009-01-01

    The human brain uncinate fasciculus (UF) is an important cortico-cortical white matter pathway that directly connects the frontal and temporal lobes, although there is a lack of conclusive support for its exact functional role. Using diffusion tensor tractography, we extracted the UF, calculated its volume and normalized it with respect to each subject’s intracranial volume (ICV) and analyzed its corresponding DTI metrics bilaterally on a cohort of 108 right-handed children and adults aged 7–68 years. Results showed inverted U-shaped curves for fractional anisotropy (FA) with advancing age and U-shaped curves for radial and axial diffusivities reflecting white matter progressive and regressive myelination and coherence dynamics that continue into young adulthood. The mean FA values of the UF were significantly larger on the left side in children (p=0.05), adults (p=0.0012) and the entire sample (p=0.0002). The FA leftward asymmetry (Left > Right) is shown to be due to increased leftward asymmetry in the axial diffusivity (p<0.0001) and a lack of asymmetry (p>0.23) for the radial diffusivity. This is the first study to provide baseline normative macro and microstructural age trajectories of the human UF across the lifespan. Results of this study may lend themselves to better understanding of UF role in future behavioral and clinical studies. PMID:19393229

  16. Progressive changes in cortical state before and after spontaneous arousals from sleep in elderly and middle-aged women.

    PubMed

    Bruce, E N; Bruce, M C; Ramanand, P; Hayes, D

    2011-02-23

    Arousals are often considered to be events which have an abrupt onset and offset, indicating abrupt changes in the state of the cortex. We hypothesized that cortical state, as reflected in electroencephalograph (EEG) signals, exhibits progressive systematic changes before and after a spontaneous, isolated arousal and that the time courses of the spectral components of the EEG before and after an arousal would differ between healthy middle-aged and elderly subjects. We analyzed the power spectrum and Sample Entropy of the C3A2 EEG before and after isolated arousals from 20 middle-aged (47.2±2.0 years) and 20 elderly (78.4±3.8 years) women using polysomnograms from the Sleep Heart Health Study database. In middle-aged women, all EEG spectral band powers <16 Hz exhibited a significant increase relative to baseline at some time in the 21 s before an arousal, but only low- (0.2-2.0 Hz) and high-frequency (2.0-4.0 Hz) delta increased in elderly and only during the last 7 s pre-arousal. Post-arousal, all frequency bands below 12 Hz transiently fell below pre-arousal baseline in both age groups. Consistent with these findings, Sample Entropy decreased steadily before an arousal, increased markedly during the arousal, and remained above pre-arousal baseline levels for ∼30 s after the arousal. In middle-aged, but not in elderly, women the presence of early pre-arousal low delta power was associated with shorter arousals. We propose that this attenuation of the effect of the arousing stimulus may be related to the slow (<1 Hz) cortical state oscillation, and that prolonged alterations of cortical state due to arousals may contribute to the poor correlation between indices of arousals and indices of sleepiness or impaired cognitive function.

  17. SEM analysis of red blood cells in aged human bloodstains.

    PubMed

    Hortolà, P

    1992-08-01

    Mammal red blood cells (RBC) in bloodstains have been previously detected by light microscopy on stone tools from as early as 100,000 +/- 25,000 years ago. In order to evaluate the degree of morphological preservation of erythrocytes in bloodstains, an accidental human blood smear on white chert and several experimental bloodstains on hard substrates (the same stone-white chert; another type of stone-graywacke; a non-stone support-stainless steel), were stored in a room, in non-sterile and fluctuating conditions, for lengths of time ranging from 3 to 18 months. Afterwards, the specimens were coated with gold and examined by a Cambridge Stereoscan 120 scanning electron microscope. Results revealed a high preservation of RBC integrity, with the maintenance of several discocytary shapes, a low tendency to echinocytosis and a frequent appearance of a moon-like erythrocytary shape in the thinner areas of the bloodstains.

  18. Added mass in human swimmers: age and gender differences.

    PubMed

    Caspersen, Cecilie; Berthelsen, Petter A; Eik, Mari; Pâkozdi, Csaba; Kjendlie, Per-Ludvik

    2010-08-26

    In unstationary swimming (changing velocity), some of the water around the swimmer is set in motion. This can be thought of as an added mass (M(a)) of water. The purpose of this study was to find added mass on human swimmers and investigate the effect of shape and body size. Thirty subjects were connected to a 2.8m long bar with handles, attached with springs (stiffness k = 318 N/m) and a force cell. By oscillating this system vertically and registering the period of oscillations it was possible to find the added mass of the swimmer, given the known masses of the bar and swimmer. Relative added mass (M(a)%) for boys, women and men were, respectively, 26.8 +/- 2.9%, 23.6 +/- 1.6% and 26.8 +/- 2.3% of the subjects total mass. This study reported significantly lower added mass (p < 0.001) and relative added mass (p < 0.002) for women compared to men, which indicate that the possible body shape differences between genders may be an important factor for determining added mass. Boys had significantly lower (p < 0.001) added mass than men. When added mass was scaled for body size there were no significant differences (p = 0.996) between boys and men, which indicated that body size is an important factor that influences added mass. The added mass in this study seems to be lower and within a smaller range than previously reported (Klauck, 1999; Eik et al., 2008). It is concluded that the added mass in human swimmers, in extended gliding position, is approximately 1/4 of the subjects' body mass.

  19. Age and Educational Selectivity among Migration and Human Capital Flows in the West.

    ERIC Educational Resources Information Center

    Evenson, James A.

    This paper quantifies and analyzes the total flows of human capital moving in and out of the West over time as a result of interregional migration. Particular emphasis is placed on analyzing the "age-education" interaction effect of migration on flows of human capital. Migration was highly selective of the young and/or highly educated…

  20. Human cognition and mobility in aging: a model for berry fruit interventions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Changes in motor function in aging, in both animals and humans, include decrements in balance, strength, and coordination, even in the absence of specific movement disorders such as Parkinson’s disease. In humans, these alterations can increase fall risk, often leading to injury and premature nursin...

  1. AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice.

    PubMed

    Zhou, Sheng; Lu, Wanli; Chen, Liang; Ge, Qiting; Chen, Dongyang; Xu, Zhihong; Shi, Dongquan; Dai, Jin; Li, Jianxin; Ju, Huangxian; Cao, Yi; Qin, Jinzhong; Chen, Shuai; Teng, Huajian; Jiang, Qing

    2017-02-22

    Osteoarthritis (OA) is a progressive degenerative disease of the joints that is associated with both joint injury and ageing. Here, we investigated the role of the energy sensor AMP-activated protein kinase (AMPK) in maintaining a healthy state of articular cartilage and in OA development. Using cartilage-specific, tamoxifen-inducible AMPKα1 conditional knockout (AMPKα1 cKO), AMPKα2 conditional knockout (AMPKα2 cKO) and AMPKα1α2 conditional double knockout (AMPKα cDKO) mice, we found that compared with wild-type (WT) littermates, mutant mice displayed accelerated severity of surgically induced OA, especially AMPKα cDKO mice. Furthermore, male but not female AMPKα cDKO mice exhibited severely spontaneous ageing-associated OA lesions at 12 months of age. The chondrocytes isolated from AMPKα cDKO mice resulted in an enhanced interleukin-1β (IL-1β)-stimulated catabolic response. In addition, upregulated expression of matrix metalloproteinase-3 (MMP-3), MMP-13 and phospho-nuclear factor-κB (phospho-NF-κB) p65 and increased levels of apoptotic markers were detected in the cartilage of AMPKα cDKO mice compared with their WT littermates in vivo. Thus, our findings suggest that AMPK activity in chondrocytes is important in maintaining joint homeostasis and OA development.

  2. AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice

    PubMed Central

    Zhou, Sheng; Lu, Wanli; Chen, Liang; Ge, Qiting; Chen, Dongyang; Xu, Zhihong; Shi, Dongquan; Dai, Jin; Li, Jianxin; Ju, Huangxian; Cao, Yi; Qin, Jinzhong; Chen, Shuai; Teng, Huajian; Jiang, Qing

    2017-01-01

    Osteoarthritis (OA) is a progressive degenerative disease of the joints that is associated with both joint injury and ageing. Here, we investigated the role of the energy sensor AMP-activated protein kinase (AMPK) in maintaining a healthy state of articular cartilage and in OA development. Using cartilage-specific, tamoxifen-inducible AMPKα1 conditional knockout (AMPKα1 cKO), AMPKα2 conditional knockout (AMPKα2 cKO) and AMPKα1α2 conditional double knockout (AMPKα cDKO) mice, we found that compared with wild-type (WT) littermates, mutant mice displayed accelerated severity of surgically induced OA, especially AMPKα cDKO mice. Furthermore, male but not female AMPKα cDKO mice exhibited severely spontaneous ageing-associated OA lesions at 12 months of age. The chondrocytes isolated from AMPKα cDKO mice resulted in an enhanced interleukin-1β (IL-1β)-stimulated catabolic response. In addition, upregulated expression of matrix metalloproteinase-3 (MMP-3), MMP-13 and phospho-nuclear factor-κB (phospho-NF-κB) p65 and increased levels of apoptotic markers were detected in the cartilage of AMPKα cDKO mice compared with their WT littermates in vivo. Thus, our findings suggest that AMPK activity in chondrocytes is important in maintaining joint homeostasis and OA development. PMID:28225087

  3. Bacteriology of Human Experimental Gingivitis: Effect of Plaque Age

    PubMed Central

    Syed, S. A.; Loesche, W. J.

    1978-01-01

    Twenty-five subjects with previously excellent hygiene and healthy gingiva developed heavy plaque accumulations and bleeding or nonbleeding gingivitis about certain papilla after 21 days of no oral hygiene. Gingival marginal plaque about a single papilla was collected at 0, 1, 2, and 3 weeks of no oral hygiene in each subject. The plaque was dispersed, serially diluted, and plated on MM10 sucrose agar in an oxygen-free atmosphere. From 50 to 100 colonies from a single high-dilution plate were characterized for each sample. Over 8,500 isolates were partially characterized and placed into one of 29 taxonomic species or groups. The flora was predominantly gram-positive at all time periods. Streptococcal species dominated in the 0- and 1-week-old plaques, i.e. 62 and 43% of the colonyforming units (CFU), but dropped to 26 to 32% of the CFU in the 2- and 3-week-old plaques. Actinomyces species dominated in the older plaques, i.e., 40 to 50% of the CFU. Actinomyces israelii was the most prominent species in the older plaques. Veillonella accounted for 15 to 20% of the CFU at all time periods. Although the other gram-negative species increased with time, collectively they averaged less than 5% of the CFU at week 3. The shift from a Streptococcus-dominated plaque to an Actinomyces-dominated plaque was the most striking microbial change observed as the plaque aged. PMID:711336

  4. Primary age-related tauopathy (PART): a common pathology associated with human aging

    PubMed Central

    Crary, John F.; Trojanowski, John Q.; Schneider, Julie A.; Abisambra, Jose F.; Abner, Erin L.; Alafuzoff, Irina; Arnold, Steven E.; Attems, Johannes; Beach, Thomas G.; Bigio, Eileen H.; Cairns, Nigel J.; Dickson, Dennis W.; Gearing, Marla; Grinberg, Lea T.; Hof, Patrick R.; Hyman, Bradley T.; Jellinger, Kurt; Jicha, Gregory A.; Kovacs, Gabor G.; Knopman, David S.; Kofler, Julia; Kukull, Walter A.; Mackenzie, Ian R.; Masliah, Eliezer; McKee, Ann; Montine, Thomas J.; Murray, Melissa E.; Neltner, Janna H.; Santa-Maria, Ismael; Seeley, William W.; Serrano-Pozo, Alberto; Shelanski, Michael L.; Stein, Thor; Takao, Masaki; Thal, Dietmar R.; Toledo, Jonathan B.; Troncoso, Juan C.; Vonsattel, Jean Paul; White, Charles L.; Wisniewski, Thomas; Woltjer, Randall L.; Yamada, Masahito; Nelson, Peter T.

    2014-01-01

    We recommend a new term, “primary age-related tauopathy” (PART), to describe a pathology that is commonly observed in the brains of aged individuals. Many autopsy studies have reported brains with neurofibrillary tangles (NFT) that are indistinguishable from those of Alzheimer's disease (AD), in the absence of amyloid (Aβ) plaques. For these “NFT+/Aβ−” brains, for which formal criteria for AD neuropathologic changes are not met, the NFT are mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas (bulb and cortex). Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment. Because cognitive impairment is often mild, existing clinicopathologic designations, such as “tangle-only dementia” and “tangle-predominant senile dementia”, are imprecise and not appropriate for most subjects. PART is almost universally detectable at autopsy among elderly individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time. Improved biomarkers and tau imaging may enable diagnosis of PART in clinical settings in the future. Indeed, recent studies have identified a common biomarker profile consisting of temporal lobe atrophy and tauopathy without evidence of Aβ accumulation. For both researchers and clinicians, a revised nomenclature will raise awareness of this extremely common pathologic change while providing a conceptual foundation for future studies. Prior reports that have elucidated features of the pathologic entity we refer to as PART are discussed, and working neuropathological diagnostic criteria are proposed. PMID:25348064

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

    PubMed

    Sohn, Elliott H; Flamme-Wiese, Miles J; Whitmore, S Scott; Wang, Kai; Tucker, Budd A; Mullins, Robert F

    2014-01-01

    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.

  6. Loss of CD34 Expression in Aging Human Choriocapillaris Endothelial Cells

    PubMed Central

    Sohn, Elliott H.; Flamme-Wiese, Miles J.; Whitmore, S. Scott; Wang, Kai; Tucker, Budd A.; Mullins, Robert F.

    2014-01-01

    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. PMID:24466138

  7. Progression Rate From Intermediate to Advanced Age-Related Macular Degeneration Is Correlated With the Number of Risk Alleles at the CFH Locus

    PubMed Central

    Sardell, Rebecca J.; Persad, Patrice J.; Pan, Samuel S.; Whitehead, Patrice; Adams, Larry D.; Laux, Reneé A.; Fortun, Jorge A.; Brantley, Milam A.; Kovach, Jaclyn L.; Schwartz, Stephen G.; Agarwal, Anita; Haines, Jonathan L.; Scott, William K.; Pericak-Vance, Margaret A.

    2016-01-01

    Purpose Progression rate of age-related macular degeneration (AMD) varies substantially, yet its association with genetic variation has not been widely examined. Methods We tested whether progression rate from intermediate AMD to geographic atrophy (GA) or choroidal neovascularization (CNV) was correlated with genotype at seven single nucleotide polymorphisms (SNPs) in the four genes most strongly associated with risk of advanced AMD. Cox proportional hazards survival models examined the association between progression time and SNP genotype while adjusting for age and sex and accounting for variable follow-up time, right censored data, and repeated measures (left and right eyes). Results Progression rate varied with the number of risk alleles at the CFH:rs10737680 but not the CFH:rs1061170 (Y402H) SNP; individuals with two risk alleles progressed faster than those with one allele (hazard ratio [HR] = 1.61, 95% confidence interval [CI] = 1.08–2.40, P < 0.02, n = 547 eyes), although this was not significant after Bonferroni correction. This signal was likely driven by an association at the correlated protective variant, CFH:rs6677604, which tags the CFHR1-3 deletion; individuals with at least one protective allele progressed more slowly. Considering GA and CNV separately showed that the effect of CFH:rs10737680 was stronger for progression to CNV. Conclusions Results support previous findings that AMD progression rate is influenced by CFH, and suggest that variants within CFH may have different effects on risk versus progression. However, since CFH:rs10737680 was not significant after Bonferroni correction and explained only a relatively small portion of variation in progression rate beyond that explained by age, we suggest that additional factors contribute to progression. PMID:27832277

  8. Between destiny and disease: genetics and molecular pathways of human central nervous system aging

    PubMed Central

    Glorioso, Christin; Sibille, Etienne

    2010-01-01

    Aging of the human brain is associated with “normal” functional, structural, and molecular changes that underlie alterations in cognition, memory, mood and motor function, amongst other processes. Normal aging also imposes a robust constraint on the onset of many neurological diseases, ranging from late onset neurodegenerative diseases, such as Alzheimer’s (AD) and Parkinson’s diseases (PD), to early onset psychiatric disorders, such as bipolar disorder (BPD) and schizophrenia (SCZ). The molecular mechanisms and genetic underpinnings of age-related changes in the brain are understudied, and, while they share some overlap with peripheral mechanisms of aging, many are unique to the largely non-mitotic brain. Hence, understanding mechanisms of brain aging and identifying associated modulators may have profound consequences for the prevention and treatment of age-related impairments and diseases. Here we review current knowledge on age-related functional and structural changes, their molecular and genetic underpinnings, and discuss how these pathways may contribute to the vulnerability to develop age-related neurological diseases. We highlight recent findings from human postmortem brain microarray studies, which we hypothesize, point to a potential genetically-controlled transcriptional program underlying molecular changes and age-gating of neurological diseases. Finally, we discuss the implications of this model for understanding basic mechanisms of brain aging and for the future investigation of therapeutic approaches. PMID:21130140

  9. General RBP expression in human tissues as a function of age.

    PubMed

    Masuda, Kiyoshi; Kuwano, Yuki; Nishida, Kensei; Rokutan, Kazuhito

    2012-09-01

    Gene expression patterns vary dramatically in a tissue-specific and age-dependent manner. RNA-binding proteins that regulate mRNA turnover and/or translation (TTR-RBPs) critically affect the subsets of expressed proteins. Although many proteins implicated in age-related processes are encoded by mRNAs that are targets of TTR-RBPs, very little is known regarding the tissue- and age-dependent expression of TTR-RBPs in humans. Recent analysis of TTR-RBPs expression using human tissue microarray has provided us interesting insight into their possibly physiologic roles as a function of age. This analysis has also revealed striking discrepancies between the levels of TTR-RBPs in senescent human diploid fibroblasts (HDFs), widely used as an in vitro model of aging, and the levels of TTR-RBPs in tissues from individuals of advancing age. In this article, we will review our knowledge of human TTR-RBP expression in different tissues as a function of age.

  10. Estrogen, not intrinsic aging, is the major regulator of delayed human wound healing in the elderly

    PubMed Central

    Hardman, Matthew J; Ashcroft, Gillian S

    2008-01-01

    Background Multiple processes have been implicated in age-related delayed healing, including altered gene expression, intrinsic cellular changes, and changes in extracellular milieu (including hormones). To date, little attempt has been made to assess the relative contribution of each of these processes to a human aging phenomenon. The objective of this study is to determine the contribution of estrogen versus aging in age-associated delayed human wound healing. Results Using an Affymetrix microarray-based approach we show that the differences in gene expression between male elderly and young human wounds are almost exclusively estrogen regulated. Expression of 78 probe sets was significantly decreased and 10 probe sets increased in wounds from elderly subjects (with a fold change greater than 7). A total of 83% of down-regulated probe sets and 80% of up-regulated probe sets were estrogen-regulated. Differentially regulated genes were validated at the level of gene and protein expression, with genes identified as estrogen-regulated in human confirmed as estrogen-dependent in young estrogen depleted mice in vivo. Moreover, direct estrogen regulation is demonstrated for three array-identified genes, Sele, Lypd3 and Arg1, in mouse cells in vitro. Conclusion These findings have clear implications for our understanding of age-associated cellular changes in the context of wound healing, the latter acting as a paradigm for other age-related repair and maintenance processes, and suggest estrogen has a more profound influence on aging than previously thought. PMID:18477406

  11. Sixty years old is the breakpoint of human frontal cortex aging.

    PubMed

    Cabré, Rosanna; Naudí, Alba; Dominguez-Gonzalez, Mayelin; Ayala, Victòria; Jové, Mariona; Mota-Martorell, Natalia; Piñol-Ripoll, Gerard; Gil-Villar, Maria Pilar; Rué, Montserrat; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2017-02-01

    Human brain aging is the physiological process which underlies as cause of cognitive decline in the elderly and the main risk factor for neurodegenerative diseases such as Alzheimer's disease. Human neurons are functional throughout a healthy adult lifespan, yet the mechanisms that maintain function and protect against neurodegenerative processes during aging are unknown. Here we show that protein oxidative and glycoxidative damage significantly increases during human brain aging, with a breakpoint at 60 years old. This trajectory is coincident with a decrease in the content of the mitochondrial respiratory chain complex I-IV. We suggest that the deterioration in oxidative stress homeostasis during aging induces an adaptive response of stress resistance mechanisms based on the sustained expression of REST, and increased or decreased expression of Akt and mTOR, respectively, over the adult lifespan in order to preserve cell neural survival and function.

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

    NASA Astrophysics Data System (ADS)

    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.

  13. Age-Infusion Approach to Derive Injury Risk Curves for Dummies from Human Cadaver Tests

    PubMed Central

    Yoganandan, Narayan; Banerjee, Anjishnu; Pintar, Frank A.

    2015-01-01

    Injury criteria and risk curves are needed for anthropomorphic test devices (dummies) to assess injuries for improving human safety. The present state of knowledge is based on using injury outcomes and biomechanical metrics from post-mortem human subject (PMHS) and mechanical records from dummy tests. Data from these models are combined to develop dummy injury assessment risk curves (IARCs)/dummy injury assessment risk values (IARVs). This simple substitution approach involves duplicating dummy metrics for PMHS tested under similar conditions and pairing with PMHS injury outcomes. It does not directly account for the age of each specimen tested in the PMHS group. Current substitution methods for injury risk assessments use age as a covariate and dummy metrics (e.g., accelerations) are not modified so that age can be directly included in the model. The age-infusion methodology presented in this perspective article accommodates for an annual rate factor that modifies the dummy injury risk assessment responses to account for the age of the PMHS that the injury data were based on. The annual rate factor is determined using human injury risk curves. The dummy metrics are modulated based on individual PMHS age and rate factor, thus “infusing” age into the dummy data. Using PMHS injuries and accelerations from side-impact experiments, matched-pair dummy tests, and logistic regression techniques, the methodology demonstrates the process of age-infusion to derive the IARCs and IARVs. PMID:26697422

  14. Age-Infusion Approach to Derive Injury Risk Curves for Dummies from Human Cadaver Tests.

    PubMed

    Yoganandan, Narayan; Banerjee, Anjishnu; Pintar, Frank A

    2015-01-01

    Injury criteria and risk curves are needed for anthropomorphic test devices (dummies) to assess injuries for improving human safety. The present state of knowledge is based on using injury outcomes and biomechanical metrics from post-mortem human subject (PMHS) and mechanical records from dummy tests. Data from these models are combined to develop dummy injury assessment risk curves (IARCs)/dummy injury assessment risk values (IARVs). This simple substitution approach involves duplicating dummy metrics for PMHS tested under similar conditions and pairing with PMHS injury outcomes. It does not directly account for the age of each specimen tested in the PMHS group. Current substitution methods for injury risk assessments use age as a covariate and dummy metrics (e.g., accelerations) are not modified so that age can be directly included in the model. The age-infusion methodology presented in this perspective article accommodates for an annual rate factor that modifies the dummy injury risk assessment responses to account for the age of the PMHS that the injury data were based on. The annual rate factor is determined using human injury risk curves. The dummy metrics are modulated based on individual PMHS age and rate factor, thus "infusing" age into the dummy data. Using PMHS injuries and accelerations from side-impact experiments, matched-pair dummy tests, and logistic regression techniques, the methodology demonstrates the process of age-infusion to derive the IARCs and IARVs.

  15. Analysis of cancer genomes reveals basic features of human aging and its role in cancer development

    PubMed Central

    Podolskiy, Dmitriy I.; Lobanov, Alexei V.; Kryukov, Gregory V.; Gladyshev, Vadim N.

    2016-01-01

    Somatic mutations have long been implicated in aging and disease, but their impact on fitness and function is difficult to assess. Here by analysing human cancer genomes we identify mutational patterns associated with aging. Our analyses suggest that age-associated mutation load and burden double approximately every 8 years, similar to the all-cause mortality doubling time. This analysis further reveals variance in the rate of aging among different human tissues, for example, slightly accelerated aging of the reproductive system. Age-adjusted mutation load and burden correlate with the corresponding cancer incidence and precede it on average by 15 years, pointing to pre-clinical cancer development times. Behaviour of mutation load also exhibits gender differences and late-life reversals, explaining some gender-specific and late-life patterns in cancer incidence rates. Overall, this study characterizes some features of human aging and offers a mechanism for age being a risk factor for the onset of cancer. PMID:27515585

  16. Effect of aging on the transverse toughness of human cortical bone: evaluation by R-curves.

    PubMed

    Koester, K J; Barth, H D; Ritchie, R O

    2011-10-01

    The age-related deterioration in the quality (e.g., strength and fracture resistance) and quantity (e.g., bone-mineral density) of human bone, together with increased life expectancy, is responsible for increasing incidence of bone fracture in the elderly. The present study describes ex vivo fracture experiments to quantitatively assess the effect of aging on the fracture toughness properties of human cortical bone specifically in the transverse (breaking) orientation. Because bone exhibits rising crack-growth resistance with crack extension, the aging-related transverse toughness is evaluated in terms of resistance-curve (R-curve) behavior, measured for bone taken from a wide range of age groups (25-74 years). Using this approach, both the ex vivo crack-initiation and crack-growth toughness are determined and are found to deteriorate with age; however, the effect is far smaller than that reported for the longitudinal toughness of cortical bone. Whereas the longitudinal crack-growth toughness has been reported to be reduced by almost an order of magnitude for human cortical bone over this age range, the corresponding age-related decrease in transverse toughness is merely ~14%. Similar to that reported for X-ray irradiated bone, with aging cracks in the transverse direction are subjected to an increasing incidence of crack deflection, principally along the cement lines, but the deflections are smaller and result in a generally less tortuous crack path.

  17. The effect of plant aging on equipment qualification and human performance issues related to license renewal

    SciTech Connect

    Gunther, W.E.; Higgins, J.C. ); Aggarwal, S.K. )

    1991-01-01

    The aging of nuclear power plants is one of the most important issues facing the nuclear industry worldwide. Aging encompasses as forms of degradation to nuclear power plant components, systems, and structures that result from exposure to environmental conditions or from operational stresses. Both the degradation from aging and actions taken to address the aging, such as increased maintenance and testing, can significantly impact human performance in the plant. Research into the causes and effects of aging as obtained through the assessment of operating experience and testing have raised questions regarding the adequacy of existing industry standards for addressing the concerns raised by this research. This paper discusses these issues, with particular emphasis in the area of equipment qualification and human performance.

  18. The effect of plant aging on equipment qualification and human performance issues related to license renewal

    SciTech Connect

    Gunther, W.E.; Higgins, J.C.; Aggarwal, S.K.

    1991-12-31

    The aging of nuclear power plants is one of the most important issues facing the nuclear industry worldwide. Aging encompasses as forms of degradation to nuclear power plant components, systems, and structures that result from exposure to environmental conditions or from operational stresses. Both the degradation from aging and actions taken to address the aging, such as increased maintenance and testing, can significantly impact human performance in the plant. Research into the causes and effects of aging as obtained through the assessment of operating experience and testing have raised questions regarding the adequacy of existing industry standards for addressing the concerns raised by this research. This paper discusses these issues, with particular emphasis in the area of equipment qualification and human performance.

  19. Functional Analyses of Human DNA Repair Proteins Important for Aging and Genomic Stability Using Yeast Genetics

    PubMed Central

    Aggarwal, Monika; Brosh, Robert M.

    2012-01-01

    Model systems have been extremely useful for studying various theories of aging. Studies of yeast have been particularly helpful to explore the molecular mechanisms and pathways that affect aging at the cellular level in the simple eukaryote. Although genetic analysis has been useful to interrogate the aging process, there has been both interest and debate over how functionally conserved the mechanisms of aging are between yeast and higher eukaryotes, especially mammalian cells. One area of interest has been the importance of genomic stability for age-related processes, and the potential conservation of proteins and pathways between yeast and human. Translational genetics have been employed to examine the functional roles of mammalian proteins using yeast as a pliable model system. In the current review recent advancements made in this area are discussed, highlighting work which shows that the cellular functions of human proteins in DNA repair and maintenance of genomic stability can be elucidated by genetic rescue experiments performed in yeast. PMID:22349084

  20. Effects of episodic future thinking on discounting: Personalized age-progressed pictures improve risky long-term health decisions.

    PubMed

    Kaplan, Brent A; Reed, Derek D; Jarmolowicz, David P

    2016-03-01

    Many everyday choices are associated with both delayed and probabilistic outcomes. The temporal attention hypothesis suggests that individuals' decision making can be improved by focusing attention on temporally distal events and implies that environmental manipulations that bring temporally distal outcomes into focus may alter an individual's degree of discounting. One such manipulation, episodic future thinking, has shown to lower discount rates; however, several questions remain about the applicability of episodic future thinking to domains other than delay discounting. The present experiments examine the effects of a modified episodic-future-thinking procedure in which participants viewed age-progressed computer-generated images of themselves and answered questions related to their future, on probability discounting in the context of both a delayed health gain and loss. Results indicate that modified episodic future thinking effectively altered individuals' degree of discounting in the predicted directions and demonstrate the applicability of episodic future thinking to decision making of socially significant outcomes.

  1. Modelling of facial growth in Czech children based on longitudinal data: Age progression from 12 to 15 years using 3D surface models.

    PubMed

    Koudelová, Jana; Dupej, Ján; Brůžek, Jaroslav; Sedlak, Petr; Velemínská, Jana

    2015-03-01

    Dealing with the increasing number of long-term missing children and juveniles requires more precise and objective age progression techniques for the prediction of their current appearance. Our contribution includes detailed and real facial growth information used for modelling age progression during adolescence. This study was based on an evaluation of the overall 180 three-dimensional (3D) facial scans of Czech children (23 boys, 22 girls), which were longitudinally studied from 12 to 15 years of age and thus revealed the real growth-related changes. The boys underwent more marked changes compared with the girls, especially in the regions of the eyebrow ridges, nose and chin. Using modern geometric morphometric methods, together with their applications, we modelled the ageing and allometric trajectories for both sexes and simulated the age-progressed effects on facial scans. The facial parts that are important for facial recognition (eyes, nose, mouth and chin) all deviated less than 0.75mm, whereas the areas with the largest deviations were situated on the marginal parts of the face. The mean error between the predicted and real facial morphology obtained by modelling the children from 12 to 15 years of age was 1.92mm in girls and 1.86mm in boys. This study is beneficial for forensic artists as it reduces the subjectivity of age progression methods.

  2. An improved syngeneic orthotopic murine model of human breast cancer progression.

    PubMed

    Rashid, Omar M; Nagahashi, Masayuki; Ramachandran, Suburamaniam; Dumur, Catherine; Schaum, Julia; Yamada, Akimitsu; Terracina, Krista P; Milstien, Sheldon; Spiegel, Sarah; Takabe, Kazuaki

    2014-10-01

    Breast cancer drug development costs nearly $610 million and 37 months in preclinical mouse model trials with minimal success rates. Despite these inefficiencies, there are still no consensus breast cancer preclinical models. Murine mammary adenocarcinoma 4T1-luc2 cells were implanted subcutaneous (SQ) or orthotopically percutaneous (OP) injection in the area of the nipple, or surgically into the chest 2nd mammary fat pad under direct vision (ODV) in Balb/c immunocompetent mice. Tumor progression was followed by in vivo bioluminescence and direct measurements, pathology and survival determined, and tumor gene expression analyzed by genome-wide microarrays. ODV produced less variable-sized tumors and was a reliable method of implantation. ODV implantation into the chest 2nd mammary pad rather than into the abdominal 4th mammary pad, the most common implantation site, better mimicked human breast cancer progression pattern, which correlated with bioluminescent tumor burden and survival. Compared to SQ, ODV produced tumors that differentially expressed genes whose interaction networks are of importance in cancer research. qPCR validation of 10 specific target genes of interest in ongoing clinical trials demonstrated significant differences in expression. ODV implantation into the chest 2nd mammary pad provides the most reliable model that mimics human breast cancer compared from subcutaneous implantation that produces tumors with different genome expression profiles of clinical significance. Increased understanding of the limitations of the different preclinical models in use will help guide new investigations and may improve the efficiency of breast cancer drug development .

  3. Neural protein gamma-synuclein interacting with androgen receptor promotes human prostate cancer progression

    PubMed Central

    2012-01-01

    Background Gamma-synuclein (SNCG) has previously been demonstrated to be significantly correlated with metastatic malignancies; however, in-depth investigation of SNCG in prostate cancer is still lacking. In the present study, we evaluated the role of SNCG in prostate cancer progression and explored the underlying mechanisms. Methods First, alteration of SNCG expression in LNCaP cell line to test the ability of SNCG on cellular properties in vitro and vivo whenever exposing with androgen or not. Subsequently, the Dual-luciferase reporter assays were performed to evaluate whether the role of SNCG in LNCaP is through AR signaling. Last, the association between SNCG and prostate cancer progression was assessed immunohistochemically using a series of human prostate tissues. Results Silencing SNCG by siRNA in LNCaP cells contributes to the inhibition of cellular proliferation, the induction of cell-cycle arrest at the G1 phase, the suppression of cellular migration and invasion in vitro, as well as the decrease of tumor growth in vivo with the notable exception of castrated mice. Subsequently, mechanistic studies indicated that SNCG is a novel androgen receptor (AR) coactivator. It interacts with AR and promotes prostate cancer cellular growth and proliferation by activating AR transcription in an androgen-dependent manner. Finally, immunohistochemical analysis revealed that SNCG was almost undetectable in benign or androgen-independent tissues prostate lesions. The high expression of SNCG is correlated with peripheral and lymph node invasion. Conclusions Our data suggest that SNCG may serve as a biomarker for predicting human prostate cancer progression and metastasis. It also may become as a novel target for biomedical therapy in advanced prostate cancer. PMID:23231703

  4. Replication licensing promotes cyclin D1 expression and G1 progression in untransformed human cells

    PubMed Central

    Liu, Peijun; Slater, Damien M.; Lenburg, Marc; Nevis, Kathleen; Cook, Jeanette Gowen; Vaziri, Cyrus

    2011-01-01

    Defects in DNA replication are implicated as early and causal events in malignancy. However, the immediate effects of impaired DNA replication licensing on cell cycle progression of non-malignant human cells are unknown. Therefore, we have investigated the acute effects of Mcm7 ablation using synchronized cultures of untransformed Human Dermal Fibroblasts (HDF). Mcm7 ablation elicited a G1 delay associated with impaired activation of CDK4 and CDK2 and reduced Rb phosphorylation. The cell cycle delay of Mcm7-ablated cells was not associated with a DNA damage response. However, levels of cyclin D1 mRNA were specifically reduced and binding of RNA Polymerase II to the CYCD1 promoter was decreased in Mcm7-depleted cells. Similar to Mcm7-deficiency, Mcm2- or Cdc6-depletion led to impaired cyclin D expression. Ectopic overexpression of Cdc6 in quiescent cells promoted cyclin D1 expression, CDK4 activation and G1 progression. Therefore timely and efficient expression of cyclin D1 during G1 phase requires replication licensing. Reconstitution of cyclin D1 expression was insufficient to correct the G1 delay of Mcm7-depleted cells, indicating that additional cell cycle events during G1 are dependent on replication licensing. However, ectopic expression of the HPV-E7 oncoprotein, and the resulting bypass of the requirement for cyclin D1-Rb signaling enabled Mcm7-depleted cells to enter S-phase. HPV-E7-induced S-phase entry of Mcm7-depleted cells led to a DNA damage response, a hallmark of pre-malignancy. Taken together, our results suggest the existence of a ‘replication licensing restriction point’ that couples pre-RC assembly with G1 progression in normal cells to minimize replication stress, DNA damage and tumorigenesis. PMID:19106611

  5. Proteolytic Activity of Human Lymphoid Tumor Cells. Correlation with Tumor Progression

    PubMed Central

    Ribatti, Domenico; Ria, Roberto; Pellegrino, Antonio; Bruno, Michele; Merchionne, Francesca; Dammacco, Franco

    2000-01-01

    Matrix metalloproteinase (MMP) expression and production are associated with advanced-stage tumor and contribute to tumor progression, invasion and metastases. The current study was designed to determine the expression and production of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) by human lymphoid tumor cells. Changes in expression and production were also investigated during tumor progression of multiple myeloma and mycosis fungoides. In situ hybridization analysis revealed that lymphoblastic leukemia B cells (SB cell line), multiple myeloma (MM) cells (U266 cell line) and lymphoblastic leukemia T cells (CEM and Jurkat cell lines) express constitutively the mRNA for MMP-2 and/or MMP-9. We demonstrated by gelatin-zymography of cell culture medium that both enzymes were secreted in their cleaved (activated) form. In situ hybridization of bone marrow plasma cells and gelatin- zymography of the medium showed that patients with active MM (diagnosis, relapse, leukemic progression) express higher levels of MMP-2 mRNA and protein than patients with non-active MM (complete/objective response, plateau) and with monoclonal gammopathies of undetermined significance (MGUS). MMP-9 expression and secretion was similar in all patient groups. In patients with mycosis fungoides (MF), the expression of MMP-2 and MMP-9 mRNAs was significantly upregulated with advancing stage, in terms of lesions both positive for one of two mRNAs and with the greatest intensity of expression. Besides MF cells, the MMP-2 and/or MMP-9 mRNAs were expressed by some stromal cell populations (microvascular endothelial cells, fibroblasts, macrophages), suggesting that these cells cooperate in the process of tumor invasion. Our studies identify MMPs as an important class of proteinases involved in the extracellular matrix (ECM) degradation by human lymphoid tumors, and suggest that MMPs inhibitors may lead to important new treatment for their control. PMID:11097203

  6. Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress.

    PubMed

    Zhang, Xiao-Liang; Pang, Wei; Hu, Xin-Tian; Li, Jia-Li; Yao, Yong-Gang; Zheng, Yong-Tang

    2014-11-18

    Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China's growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China's life sciences and pharmaceutical industry, and enhance China's position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China.

  7. Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress

    PubMed Central

    ZHANG, Xiao-Liang; PANG, Wei; HU, Xin-Tian; LI, Jia-Li; YAO, Yong-Gang; ZHENG, Yong-Tang

    2014-01-01

    Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China’s growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China’s life sciences and pharmaceutical industry, and enhance China’s position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China. PMID:25465081

  8. Age and Amyloid Effects on Human CNS Amyloid-Beta Kinetics

    PubMed Central

    Patterson, Bruce W.; Elbert, Donald L.; Mawuenyega, Kwasi G.; Kasten, Tom; Ovod, Vitaliy; Ma, Shengmei; Xiong, Chengjie; Chott, Robert; Yarasheski, Kevin; Sigurdson, Wendy; Zhang, Lily; Goate, Alison; Phil, D.; Benzinger, Tammie; Morris, John C.; Holtzman, David; Bateman, Randall J.

    2015-01-01

    Objective Age is the single greatest risk factor for Alzheimer’s disease with the incidence doubling every 5 years after age 65. However, our understanding of the mechanistic relationship between increasing age and the risk for Alzheimer’s disease is currently limited. We therefore sought to determine the relationship between age, amyloidosis, and amyloid-beta kinetics in the central nervous system (CNS) of humans Methods Amyloid-beta kinetics were analyzed in 112 participants and compared to the ages of participants and the amount of amyloid deposition. Results We found a highly significant correlation between increasing age and slowed amyloid-beta turnover rates (2.5-fold longer half-life over five decades of age). In addition, we found independent effects on amyloid-beta42 kinetics specifically in participants with amyloid deposition. Amyloidosis was associated with a higher (>50%) irreversible loss of soluble amyloid-beta42 and a 10-fold higher amyloid-beta42 reversible exchange rate. Interpretation These findings reveal a mechanistic link between human aging and the risk of amyloidosis which may be due to a dramatic slowing of amyloid-beta turnover, increasing the likelihood of protein misfolding that leads to deposition. Alterations in amyloid-beta kinetics associated with aging and amyloidosis suggest opportunities for diagnostic and therapeutic strategies. More generally, this study provides an example of how changes in protein turnover kinetics can be used to detect physiologic and pathophysiologic changes and may be applicable to other proteinopathies. PMID:26040676

  9. Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts

    PubMed Central

    Huh, Christine J; Zhang, Bo; Victor, Matheus B; Dahiya, Sonika; Batista, Luis FZ; Horvath, Steve; Yoo, Andrew S

    2016-01-01

    Aging is a major risk factor in many forms of late-onset neurodegenerative disorders. The ability to recapitulate age-related characteristics of human neurons in culture will offer unprecedented opportunities to study the biological processes underlying neuronal aging. Here, we show that using a recently demonstrated microRNA-based cellular reprogramming approach, human fibroblasts from postnatal to near centenarian donors can be efficiently converted into neurons that maintain multiple age-associated signatures. Application of an epigenetic biomarker of aging (referred to as epigenetic clock) to DNA methylation data revealed that the epigenetic ages of fibroblasts were highly correlated with corresponding age estimates of reprogrammed neurons. Transcriptome and microRNA profiles reveal genes differentially expressed between young and old neurons. Further analyses of oxidative stress, DNA damage and telomere length exhibit the retention of age-associated cellular properties in converted neurons from corresponding fibroblasts. Our results collectively demonstrate the maintenance of age after neuronal conversion. DOI: http://dx.doi.org/10.7554/eLife.18648.001 PMID:27644593

  10. Aging and DNA damage in humans: a meta-analysis study

    PubMed Central

    Soares, Jorge Pinto; Cortinhas, António; Bento, Teresa; Leitão, José Carlos; Collins, Andrew R.; Gaivã, Isabel; Mota, Maria Paula

    2014-01-01

    Age-related DNA damage is regarded as one of the possible explanations of aging. Although a generalized idea about the accumulation of DNA damage with age exists, results found in the literature are inconsistent. To better understand the question of age-related DNA damage in humans and to identify possible moderator variables, a meta-analysis was conducted. Electronic databases and bibliographies for studies published since 2004 were searched. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for age-related DNA damage were calculated in a random-effects model. A total of 76 correlations from 36 studies with 4676 participants were included. Based on our analysis, a correlation between age and DNA damage was found (r = 0.230, p = 0.000; 95% confidence interval = 0.111 - 0.342). The test for heterogeneity of variance indicates that the study´s results are significantly high (Q (75) = 1754.831, p = 0.000). Moderator variables such as smoking habits, technique used, and the tissue/sample analyzed, are shown to influence age-related DNA damage (p=0.026; p=0.000; p=0.000, respectively). Nevertheless, sex did not show any influence on this relation (p=0.114). In conclusion, this meta-analysis showed an association between age and DNA damage in humans. It was also found that smoking habits, the technique used, and tissue/sample analyzed, are important moderator variables in age-related DNA damage. PMID:25140379

  11. Diverse Roles of Growth Hormone and Insulin-Like Growth Factor-1 in Mammalian Aging: Progress and Controversies

    PubMed Central

    Csiszar, Anna; de Cabo, Raphael; Ferrucci, Luigi; Ungvari, Zoltan

    2012-01-01

    Because the initial reports demonstrating that circulating growth hormone and insulin-like growth factor-1 decrease with age in laboratory animals and humans, there have been numerous studies related to the importance of these hormones for healthy aging. Nevertheless, the role of these potent anabolic hormones in the genesis of the aging phenotype remains controversial. In this chapter, we review the studies demonstrating the beneficial and deleterious effects of growth hormone and insulin-like growth factor-1 deficiency and explore their effects on specific tissues and pathology as well as their potentially unique effects early during development. Based on this review, we conclude that the perceived contradictory roles of growth hormone and insulin-like growth factor-1 in the genesis of the aging phenotype should not be interpreted as a controversy on whether growth hormone or insulin-like growth factor-1 increases or decreases life span but rather as an opportunity to explore the complex roles of these hormones during specific stages of the life span. PMID:22522510

  12. Diverse roles of growth hormone and insulin-like growth factor-1 in mammalian aging: progress and controversies.

    PubMed

    Sonntag, William E; Csiszar, Anna; deCabo, Raphael; Ferrucci, Luigi; Ungvari, Zoltan

    2012-06-01

    Because the initial reports demonstrating that circulating growth hormone and insulin-like growth factor-1 decrease with age in laboratory animals and humans, there have been numerous studies related to the importance of these hormones for healthy aging. Nevertheless, the role of these potent anabolic hormones in the genesis of the aging phenotype remains controversial. In this chapter, we review the studies demonstrating the beneficial and deleterious effects of growth hormone and insulin-like growth factor-1 deficiency and explore their effects on specific tissues and pathology as well as their potentially unique effects early during development. Based on this review, we conclude that the perceived contradictory roles of growth hormone and insulin-like growth factor-1 in the genesis of the aging phenotype should not be interpreted as a controversy on whether growth hormone or insulin-like growth factor-1 increases or decreases life span but rather as an opportunity to explore the complex roles of these hormones during specific stages of the life span.

  13. Aging and immunosenescence in invertebrates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most contemporary research into aging is driven by interest in the human aging process and in interventions that attenuate the normal and pathophysiological effects of aging, or senescence. Operationally, senescence is the progressive, inevitable breakdown of the organism. Among the changes associat...

  14. Rejuvenation of Gene Expression Pattern of Aged Human Skin by Broadband Light Treatment: A Pilot Study

    PubMed Central

    Chang, Anne Lynn S; Bitter, Patrick H; Qu, Kun; Lin, Meihong; Rapicavoli, Nicole A; Chang, Howard Y

    2013-01-01

    Studies in model organisms suggest that aged cells can be functionally rejuvenated, but whether this concept applies to human skin is unclear. Here we apply 3′-end sequencing for expression quantification (“3-seq”) to discover the gene expression program associated with human photoaging and intrinsic skin aging (collectively termed “skin aging”), and the impact of broadband light (BBL) treatment. We find that skin aging was associated with a significantly altered expression level of 2,265 coding and noncoding RNAs, of which 1,293 became “rejuvenated” after BBL treatment; i.e., they became more similar to their expression level in youthful skin. Rejuvenated genes (RGs) included several known key regulators of organismal longevity and their proximal long noncoding RNAs. Skin aging is not associated with systematic changes in 3′-end mRNA processing. Hence, BBL treatment can restore gene expression pattern of photoaged and intrinsically aged human skin to resemble young skin. In addition, our data reveal, to our knowledge, a previously unreported set of targets that may lead to new insights into the human skin aging process. PMID:22931923

  15. Polarization sensitive changes in the human macula associated with normal aging and age-related macular degeneration

    NASA Astrophysics Data System (ADS)

    VanNasdale, Dean Allan, Jr.

    2011-12-01

    The human macula occupies a relatively small, but crucial retinal area, as it is the location responsible for our most acute spatial vision and best color discrimination. Localizing important landmarks in the retina is difficult even in normal eyes where morphological inter-individual variability is high. This becomes even more challenging in the presence of sight-threatening pathology. With respect to the human macula, there remains a significant gap in the understanding of normal structure and function. Even less is known about the pathological mechanisms that occur in sight-threatening diseases including age-related macular degeneration. Because relatively little is known about normal aging changes, it is also difficult to differentiate those changes from changes associated with retinal disease. To better understand normal and pathological changes in the macula, imaging techniques using specific optical signatures are required. Structural features in the macula can be distinguished based on their intrinsic properties using specific light/tissue interactions. Because of the high degree of structural regularity in the macula, polarization sensitive imaging is potentially a useful tool for evaluating the morphology and integrity of the cellular architecture for both normal individuals and those affected by disease. In our investigations, we used polarization sensitive imaging to determining normal landmarks that are important clinically and for research investigations. We found that precision and accuracy in localizing the central macula was greatly improved through the use of polarization sensitive imaging. We also found that specific polarization alterations can be used to demonstrate systematic changes as a function of age, disproportionately affecting the central macular region. When evaluating patients with age-related macular degeneration, we found that precision and accuracy of localizing the central macula was also improved, even when significant pathology

  16. Determination of Human Hepatic CYP2C8 and CYP1A2 Age-Dependent Expression to Support Human Health Risk Assessment for Early Ages.

    PubMed

    Song, Gina; Sun, Xueying; Hines, Ronald N; McCarver, D Gail; Lake, Brian G; Osimitz, Thomas G; Creek, Moire R; Clewell, Harvey J; Yoon, Miyoung

    2017-02-22

    Predicting age-specific metabolism is important for evaluating age-related drug and chemical sensitivity. Multiple cytochrome P450s (CYP) and carboxylesterase (CES) enzymes are responsible for human pyrethroid metabolism. Complete ontogeny data for each enzyme is needed to support in vitro to in vivo extrapolation (IVIVE). This study was designed to determine age-dependent human hepatic CYP2C8 expression, for which only limited ontogeny data are available, and to further define CYP1A2 ontogeny. CYP2C8 and 1A2 protein levels were measured by quantitative Western blotting using liver microsomal samples prepared from 222 subjects with ages ranging from 8 weeks gestation to 18 years after birth. The median CYP2C8 expression was significantly greater among samples from subjects older than 35 postnatal days (n=122) compared to fetal samples and those from very young infants (fetal to 35 days postnatal, n=100) (0.00 vs. 13.38 pmol/mg microsomal protein; p<0.0001). In contrast, the median CYP1A2 expression was significantly greater after 15 months postnatal age (n=55) than in fetal and younger postnatal samples (fetal to 15 months postnatal, n=167) (0.0167 vs. 2.354 pmol/mg microsomal protein; p<0.0001). CYP2C8, but not CYP1A2, protein levels, significantly correlated with those of CYP2C9, CYP2C19, and CYP3A4 (p<0.001) consistent with CYP2C8 and CYP1A2 ontogeny being probably controlled by different mechanisms. This study provides key data for physiologically based pharmacokinetic model-based prediction of age-dependent pyrethroid metabolism, which will be used for IVIVE to support pyrethroid risk assessment for early life stages.

  17. The effect of moesin overexpression on ageing of human dermal microvascular endothelial cells.

    PubMed

    Lee, Ju Hee; Hong, In Ae; Oh, Sang Ho; Kwon, Yeon Sook; Cho, Soo Hyun; Lee, Kwang Hoon

    2009-11-01

    Senescence of microvascular endothelial cells is known to play an important role in the pathophysiology of vascular diseases related to ageing, but the accurate mechanism or related genes are not known. Moesin, a cytoskeletal protein and the most potent candidate as an ageing-related protein, showed obvious changes in expression when compared before and after ageing. In this study, a lentivirus was used to overexpress moesin in endothelial cells. The expression of cell cycle mediators such as p16, cyclin D1 and cdk4, which can be the markers of ageing, was compared by RNA and was shown to be suppressed in moesin overexpressed endothelial cells. In conclusion, it can be said that the expression of moesin delays senescence of human dermal microvascular endothelial cells and this fundamental discovery can be used as a basis for understanding the mechanism of ageing and age-related diseases.

  18. Heightened muscle inflammation susceptibility may impair regenerative capacity in aging humans

    PubMed Central

    Merritt, Edward K.; Stec, Michael J.; Thalacker-Mercer, Anna; Windham, Samuel T.; Cross, James M.; Shelley, David P.; Craig Tuggle, S.; Kosek, David J.; Kim, Jeong-su

    2013-01-01

    The regenerative response of skeletal muscle to mechanically induced damage is impaired with age. Previous work in our laboratory suggests this may result from higher proinflammatory signaling in aging muscle at rest and/or a greater inflammatory response to damage. We, therefore, assessed skeletal muscle proinflammatory signaling at rest and 24 h after unaccustomed, loaded knee extension contractions that induced modest muscle damage (72% increase in serum creatine kinase) in a cohort of 87 adults across three age groups (AGE40, AGE61, and AGE76). Vastus lateralis muscle gene expression and protein cell signaling of the IL-6 and TNF-α pathways were determined by quantitative PCR and immunoblot analysis. For in vitro studies, cell signaling and fusion capacities were compared among primary myoblasts from young (AGE28) and old (AGE64) donors treated with TNF-α. Muscle expression was higher (1.5- to 2.1-fold) in AGE76 and AGE61 relative to AGE40 for several genes involved in IL-6, TNF-α, and TNF-like weak inducer of apoptosis signaling. Indexes of activation for the proinflammatory transcription factors signal transducer and activator of transcription-3 and NF-κB were highest in AGE76. Resistance loading reduced gene expression of IL-6 receptor, muscle RING finger 1, and atrogin-1, and increased TNF-like weak inducer of apoptosis receptor expression. Donor myoblasts from AGE64 showed impaired differentiation and fusion in standard media and greater NF-κB activation in response to TNF-α treatment (compared with AGE28). We show for the first time that human aging is associated with muscle inflammation susceptibility (i.e., higher basal state of proinflammatory signaling) that is present in both tissue and isolated myogenic cells and likely contributes to the impaired regenerative capacity of skeletal muscle in the older population. PMID:23681911

  19. Age-related impairments in discriminating perceptually similar objects parallel those observed in humans.

    PubMed

    Johnson, Sarah A; Turner, Sean M; Santacroce, Lindsay A; Carty, Katelyn N; Shafiq, Leila; Bizon, Jennifer L; Maurer, Andrew P; Burke, Sara N

    2017-03-25

    The ability to accurately remember distinct episodes is supported by high-level sensory discrimination. Performance on mnemonic similarity tasks, which test high-level discrimination, declines with advancing age in humans and these deficits have been linked to altered activity in hippocampal CA3 and dentate gyrus. Lesion studies in animal models, however, point to the perirhinal cortex as a brain region critical for sensory discriminations that serve memory. Reconciliation of the contributions of different regions within the cortical-hippocampal circuit requires the development of a discrimination paradigm comparable to the human mnemonic similarity task that can be used in rodents. In the present experiments, young and aged rats were cross-characterized on a spatial water maze task and two variants of an object discrimination task: one in which rats incrementally learned which object of a pair was rewarded and different pairs varied in their similarity (Experiment 1), and a second in which rats were tested on their ability to discriminate a learned target object from multiple lure objects with an increasing degree of feature overlap (Experiment 2). In Experiment 1, aged rats required more training than young to correctly discriminate between similar objects. Comparably, in Experiment 2, aged rats were impaired in discriminating a target object from lures when the pair shared more features. Discrimination deficits across experiments were correlated within individual aged rats, though, for the cohort tested, aged rats were not impaired overall in spatial learning and memory. This could suggest discrimination deficits emerging with age precede declines in spatial or episodic memory, an observation that has been made in humans. Findings of robust impairments in object discrimination abilities in the aged rats parallel results from human studies, supporting use of the developed tasks for mechanistic investigation of cortical-hippocampal circuit dysfunction in aging and

  20. Age Progression of Neuropathological Markers in the Brain of the Chilean Rodent Octodon degus, a Natural Model of Alzheimer's Disease.

    PubMed

    Inestrosa, Nibaldo C; Ríos, Juvenal A; Cisternas, Pedro; Tapia-Rojas, Cheril; Rivera, Daniela S; Braidy, Nady; Zolezzi, Juan M; Godoy, Juan A; Carvajal, Francisco J; Ardiles, Alvaro O; Bozinovic, Francisco; Palacios, Adrián G; Sachdev, Perminder S

    2015-11-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder and the leading cause of age-related dementia worldwide. Several models for AD have been developed to provide information regarding the initial changes that lead to degeneration. Transgenic mouse models recapitulate many, but not all, of the features of AD, most likely because of the high complexity of the pathology. In this context, the validation of a wild-type animal model of AD that mimics the neuropathological and behavioral abnormalities is necessary. In previous studies, we have reported that the Chilean rodent Octodon degus could represent a natural model for AD. In the present work, we further describe the age-related neurodegeneration observed in the O. degus brain. We report some histopathological markers associated with the onset progression of AD, such as glial activation, increase in oxidative stress markers, neuronal apoptosis and the expression of the peroxisome proliferative-activated receptor γ coactivator-1α (PGC-1α). With these results, we suggest that the O. degus could represent a new model for AD research and a powerful tool in the search for therapeutic strategies against AD.

  1. Progress and Challenges in Developing Metabolic Footprints from Diet in Human Gut Microbial Cometabolism12

    PubMed Central

    Duffy, Linda C; Raiten, Daniel J; Hubbard, Van S; Starke-Reed, Pamela

    2015-01-01

    Homo sapiens harbor trillions of microbes, whose microbial metagenome (collective genome of a microbial community) using omic validation interrogation tools is estimated to be at least 100-fold that of human cells, which comprise 23,000 genes. This article highlights some of the current progress and open questions in nutrition-related areas of microbiome research. It also underscores the metabolic capabilities of microbial fermentation on nutritional substrates that require further mechanistic understanding and systems biology approaches of studying functional interactions between diet composition, gut microbiota, and host metabolism. Questions surrounding bacterial fermentation and degradation of dietary constituents (particularly by Firmicutes and Bacteroidetes) and deciphering how microbial encoding of enzymes and derived metabolites affect recovery of dietary energy by the host are more complex than previously thought. Moreover, it is essential to understand to what extent the intestinal microbiota is subject to dietary control and to integrate these data with functional metabolic signatures and biomarkers. Many lines of research have demonstrated the significant role of the gut microbiota in human physiology and disease. Probiotic and prebiotic products are proliferating in the market in response to consumer demand, and the science and technology around these products are progressing rapidly. With high-throughput molecular technologies driving the science, studying the bidirectional interactions of host-microbial cometabolism, epithelial cell maturation, shaping of innate immune development, normal vs. dysfunctional nutrient absorption and processing, and the complex signaling pathways involved is now possible. Substantiating the safety and mechanisms of action of probiotic/prebiotic formulations is critical. Beneficial modulation of the human microbiota by using these nutritional and biotherapeutic strategies holds considerable promise as next

  2. Muscarinic acetylcholine receptors regulating cell cycle progression are expressed in human gingival keratinocytes.

    PubMed

    Arredondo, J; Hall, L L; Ndoye, A; Chernyavsky, A I; Jolkovsky, D L; Grando, S A

    2003-02-01

    We have previously reported the presence in human gingival keratinocytes (GKC) of choline acetyltransferase, the acetylcholine (ACh) synthesizing enzyme, acetylcholinesterase, the ACh degrading enzyme, and alpha 3, alpha 5, alpha 7, beta 2 as well as alpha 9 nicotinic ACh receptor subunits. To expand the knowledge about the role of ACh in oral biology, we investigated the presence of the muscarinic ACh receptor (mAChR) subtypes in GKC. RT-PCR demonstrated the presence of m2, m3, m4, and m5 mRNA transcripts. Synthesis of the respective proteins was verified by immunoblotting with the subtype-specific antibodies that revealed receptor bands at the expected molecular weights. The antibodies mapped mAChR subtypes in the epithelium of human attached gingiva and also visualized them on the cell membrane of cultured GKC. The whole cell radioligand binding assay revealed that GKC have specific binding sites for the muscarinic ligand [3H]quinuclidinyl benzilate, Bmax = 222.9 fmol/106 cells with a Kd of 62.95 pM. The downstream coupling of the mAChRs to regulation of cell cycle progression in GKC was studied using quantitative RT-PCR and immunoblotting assays. Incubation of GKC for 24 h with 10 micro m muscarine increased relative amounts of Ki-67, PCNA and p53 mRNAs and PCNA, cyclin D1, p21 and p53 proteins. These effects were abolished in the presence of 50 micro m atropine. The finding in GKC of mAChRs coupled to regulation of the cell cycle progression demonstrate further the structure/function of the non-neuronal cholinergic system operating in human oral epithelium. The results obtained in this study help clarify the role for keratinocyte ACh axis in the physiologic control of oral gingival homeostasis.

  3. Cellular morphometry of the bronchi of human and dog lungs. Progress report, April 1, 1991--October 1, 1991

    SciTech Connect

    Robbins, E.S.

    1991-09-01

    One hundred and forty-seven bronchial samples (generations 3--6) from 66 patients (62 usable; 36 female, 26 male; median age 61) have been dissected by generation from fixed surgical lung specimens obtained after the removal of pathological lesions. In addition, one hundred and fifty-six mongol dog bronchi (generations 2--6) dissected from different lobes of 26 dog lungs have also been similarly prepared. One hundred and twenty-seven human samples have been completely processed for electron microscopy and have yielded 994 electron micrographs of which 655 have been entered into the Computerized Stereological Analysis System (COSAS) and been used for the measurement of the distances of basal and mucous cell nuclei to the epithelial free surface. Similarly 328 micrographs of dog epithelium from 33 bronchial samples have been used to measure the distances of basal and mucous cell nuclei to the epithelial free surface and have been entered into COSAS. Using the COSAS planimetry program, we continue to expand our established data bases which describe the volume density and nuclear numbers per electron micrograph for 5 cell types of the human bronchial epithelial lining of men and women, as well as smokers, non-smokers and ex-smokers and similar parameters for the same 5 epithelial cell types of dog bronchi. Our micrographs of human bronchial epithelium have allowed us to analyze the recent suggestion that the DNA of lymphocytes may be subject to significant damage from Rn progeny while within the lung. Since the last progress report three papers have been submitted for publication. 17 refs., 4 tabs.

  4. Collagen cross-linking effect on progressive keratoconus in patients younger than 18 years of age: A clinical trial

    PubMed Central

    Peyman, Alireza; Kamali, Ali; Khushabi, Maral; Nasrollahi, Kobra; Kargar, Neda; Taghaodi, Maryam; Razmjoo, Hasan; Fazel, Farhad; Salesi, Asiyeh

    2015-01-01

    Background: Keratoconus is a bilateral non-inflammatory corneal disease. Collagen cross-linking (CXL) is a new treatment option for the disease that uses ultraviolet A light irradiation and riboflavin administration. The aim of this study is to evaluate the effect of CXL on corneal topographic and refractive values in patients with keratoconus younger than 18 years of age. Materials and Methods: For the clinical trial study, 37 patients (64 eyes) younger than 18 years of age with progressive keratoconus were included. Age, sex, family history of keratoconus, and history of allergic disorders and eye rubbing were recorded. Refractive, topographic, and topometric indices were evaluated before and 12 months after the CXL with 3mW for 30 minutes. Results: Mean age (±SD) of the patients was 15.83 ± 1.53 years; 26 (70.3%) of the 37 patients were male. Fourteen (37.8%) had positive family history of keratoconus, 11 (29.7%) had history of allergic disorders, and 15 (40.5%) had positive history of eye rubbing. Of the refractive values, cylinder value decreased significantly from −4.50 ± 0.29 to −4.11 ± 0.28 (P = 0.001). Also, the logarithm of minimal angle of resolution (logMAR) uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) improved significantly 12 months after CXL (P = 0.012 and 0.001, respectively). Maximum keratometry before and after the operation was 53.82 ± 0.72 and 53.33 ± 0.72, respectively (P = 0.018). Differences for simulated K values, the thinnest cornea pachymetry, keratoconus index (KI), index of highest asymmetry (IHA), and index of highest decentration (IHD) before and 12 months after the CXL were statistically significant (P = 0.015, 0.034, <0.001, 0.017, 0.019, and 0.004, respectively). Conclusion: CXL improves the refractory, topographic, and topometric indices in patients with keratoconus younger than 18 years of age. PMID:26693470

  5. Risk Factors for Four-Year Incidence and Progression of Age-Related Macular Degeneration: The Los Angeles Latino Eye Study

    PubMed Central

    CHOUDHURY, FARZANA; VARMA, ROHIT; MCKEAN-COWDIN, ROBERTA; KLEIN, RONALD; AZEN, STANLEY P.

    2011-01-01

    PURPOSE To identify risk factors for 4-year incidence and progression of age-related macular degeneration (AMD) in adult Latinos. DESIGN Population-based prospective cohort study. METHODS Participants, aged 40 or older, from The Los Angeles Latino Eye Study (LALES) underwent standardized comprehensive ophthalmologic examinations at baseline and at 4 years of follow-up. Age-related macular degeneration was detected by grading 30-degree stereoscopic fundus photographs using the modified Wisconsin Age-Related Maculopathy Grading System. Multivariate stepwise logistic regression was used to examine the independent association of incidence and progression of AMD and baseline sociodemographic, behavioral, clinical, and ocular characteristics. RESULTS Multivariate analyses revealed that older age (OR per decade of age: 1.52; 95% CI: 1.29, 1.85) and higher pulse pressure (OR per 10 mm Hg: 2.54; 95% CI: 1.36, 4.76) were independently associated with the incidence of any AMD. The same factors were associated with early AMD, soft indistinct drusen, and retinal pigmentary abnormalities. Additionally, presence of clinically diagnosed diabetes mellitus was independently associated with increased retinal pigment (OR: 1.66; 95% CI: 1.01, 2.85), and male gender was associated with retinal pigment epithelial depigmentation (OR 2.50; 95% CI: 1.48, 4.23). Older age (OR per decade of age: 2.20; 95% CI: 1.82, 2.67) and current smoking (OR: 2.85; 95% CI: 1.66, 4.90) were independently associated with progression of AMD. CONCLUSIONS Several modifiable risk factors were associated with 4-year incidence and progression of AMD in Latinos. The results suggest that interventions aimed at reducing pulse pressure and promoting smoking cessation may reduce incidence and progression of AMD, respectively. PMID:21679916

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

    PubMed

    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.

  7. Laser treatment of drusen to prevent progression to advanced age-related macular degeneration

    PubMed Central

    Virgili, Gianni; Michelessi, Manuele; Parodi, Maurizio B; Bacherini, Daniela; Evans, Jennifer R

    2016-01-01

    Background Drusen are amorphous yellowish deposits beneath the sensory retina. People with drusen, particularly large drusen, are at higher risk of developing age-related macular degeneration (AMD). The most common complication in AMD is choroidal neovascularisation (CNV), the growth of new blood vessels in the centre of the macula. The risk of CNV is higher among people who are already affected by CNV in one eye. It has been observed clinically that laser photocoagulation of drusen leads to their disappearance and may prevent the occurrence of advanced disease (CNV or geographic atrophy) associated with visual loss. Objectives To examine the effectiveness and adverse effects of laser photocoagulation of drusen in AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2015), EMBASE (January 1980 to August 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 3 August 2015. Selection criteria Randomised controlled trials (RCTs) of laser treatment of drusen in AMD in which laser treatment had been compared with no intervention or sham treatment. Two types of trials were included. Some trials studied one eye of each participant (unilateral studies); other studies recruited participants with bilateral drusen and randomised one eye to photocoagulation or control and the fellow eye to the other group. Data collection and analysis Two review authors independently

  8. The impact of age at death on the lag time of radiocarbon values in human bone.

    PubMed

    Ubelaker, Douglas H; Thomas, Christian; Olson, Jacqueline E

    2015-06-01

    Analysis of modern bomb-pulse radiocarbon in human bone offers data needed to interpret the post-mortem interval in skeletonized human remains recovered from forensic contexts. Radiocarbon analysis of different tissues with distinct rates of remodeling allows proper placement of the values on the modern bomb-curve. However, the lag time between the date of intercept on the curve and the actual death date is largely affected by the age at death. Published data on radiocarbon analysis of individuals of known age at death and death dates indicate that this lag time increases with age until about 60 years. The lag time documented for each decade of life can be used to compensate for this age-related factor and increase the accuracy of interpretation of the death date. While this method could be greatly improved by original research with a larger sample size, this study provides an adequate point from which to launch further investigations into the subject.

  9. Aging Shapes the Population-Mean and -Dispersion of Gene Expression in Human Brains

    PubMed Central

    Brinkmeyer-Langford, Candice L.; Guan, Jinting; Ji, Guoli; Cai, James J.

    2016-01-01

    Human aging is associated with cognitive decline and an increased risk of neurodegenerative disease. Our objective for this study was to evaluate potential relationships between age and variation in gene expression across different regions of the brain. We analyzed the Genotype-Tissue Expression (GTEx) data from 54 to 101 tissue samples across 13 brain regions in post-mortem donors of European descent aged between 20 and 70 years at death. After accounting for the effects of covariates and hidden confounding factors, we identified 1446 protein-coding genes whose expression in one or more brain regions is correlated with chronological age at a false discovery rate of 5%. These genes are involved in various biological processes including apoptosis, mRNA splicing, amino acid biosynthesis, and neurotransmitter transport. The distribution of these genes among brain regions is uneven, suggesting variable regional responses to aging. We also found that the aging response of many genes, e.g., TP37 and C1QA, depends on individuals' genotypic backgrounds. Finally, using dispersion-specific analysis, we identified genes such as IL7R, MS4A4E, and TERF1/TERF2 whose expressions are differentially dispersed by aging, i.e., variances differ between age groups. Our results demonstrate that age-related gene expression is brain region-specific, genotype-dependent, and associated with both mean and dispersion changes. Our findings provide a foundation for more sophisticated gene expression modeling in the studies of age-related neurodegenerative diseases. PMID:27536236

  10. Sexual dimorphism of facial appearance in ageing human adults: A cross-sectional study.

    PubMed

    Mydlová, Miriama; Dupej, Ján; Koudelová, Jana; Velemínská, Jana

    2015-12-01

    In the forensic sciences, knowledge of facial ageing is very important in searching for both dead and living individuals. Ageing estimations typically model the biological profile, which can be compared to missing persons. The main goals of this current study were to construct ageing trajectories for adult human faces of both sexes and evaluate sexual dimorphism in relation to static allometry. Our study was based on the analysis of three-dimensional facial surface models of 194 individuals 20-80 years of age. The evaluation consisted of a dense correspondence analysis of facial scans and multivariate statistics. It was shown that both age and sex have a significant influence on facial form and shape. Male features included a longer face, with more protruded foreheads, eyebrow ridges and nose, including the region under the upper lip and mandible region, but more retruded cheeks compared to females. Ageing in both sexes shared common traits, such as more pronounced roundness of the face (rectangular in males), decreased facial convexity, increased visibility of skin folds and wrinkles connected with the loss of skin elasticity, and soft tissue stretching, especially in the orbital area and lower face; however, male faces exhibited more intense ageing changes. The above-mentioned sexual dimorphic traits tended to diminish in the elderly age category, though overall sexual dimorphism was heightened with age. The static allometric relationships between size and form or shape were similar in both sexes, except that the larger faces of elderly males displayed more intensive ageing changes.

  11. Age estimation methods using anthropological parameters on human teeth-(A0736).

    PubMed

    Brkic, H; Milicevic, M; Petrovecki, M

    2006-10-16

    The research was conducted on the 160 intact extracted human teeth with one and two roots of the known age and sex. The teeth were disinfected, dried and X-rayed. After that the section of the longitudinal cut through the teeth was performed in order to facilitate monitoring of all tissues and morphological characteristics of the teeth. The age was determined in three ways: Method 1 [G.Bang, E. Ramm, Determination of age in humans from root dentin transparency, Acta Odontol. Scand. 28 (1970) 3-35]--analysis of the translucency of the root dentine, Method 2 [S. Kvaal, T. Solheim, A non-destructive dental method for age estimation, J. Forensic Odonto-stomatol. 12 (1994) 6-11]--analysis of the root and the root canal from the X-ray, Method 3 [G. Johanson, Age determination from human teeth, Odontol. Revy. 22 (1971) 1-126]--analysis of six parameters on each teeth. All data were subject to the correlation and regression analysis which showed the following: all of the three applied methods were in the significant correlation with the real age, and the best of them proved to be Method 3 where the coefficient of correlation was 0.85, p<0.001. The teeth of the maxilla are more convenient for the age determination than the teeth of mandible. They are in the significant strong correlation with the known real age, and in Method 3, the coefficient of correlation is 0.78, p<0.001. Age determination of the teeth with two roots is in significant correlation with the known real age p<0.001 in relation to the determined age on the teeth with one root. The results show that sex too, is in significant correlation with the real age, p<0.001. In practice, the methods used and the results achieved in this research have been enabling the dental age estimation of human remains from mass graves after the 1991 war in Croatia.

  12. Role of the cystathionine γ lyase/hydrogen sulfide pathway in human melanoma progression.

    PubMed

    Panza, Elisabetta; De Cicco, Paola; Armogida, Chiara; Scognamiglio, Giosuè; Gigantino, Vincenzo; Botti, Gerardo; Germano, Domenico; Napolitano, Maria; Papapetropoulos, Andreas; Bucci, Mariarosaria; Cirino, Giuseppe; Ianaro, Angela

    2015-01-01

    In humans, two main metabolic enzymes synthesize hydrogen sulfide (H2 S): cystathionine γ lyase (CSE) and cystathionine β synthase (CBS). A third enzyme, 3-mercaptopyruvate sulfurtransferase (3-MST), synthesizes H2 S in the presence of the substrate 3-mercaptopyruvate (3-MP). The immunohistochemistry analysis performed on human melanoma samples demonstrated that CSE expression was highest in primary tumors, decreased in the metastatic lesions and was almost silent in non-lymph node metastases. The primary role played by CSE was confirmed by the finding that the overexpression of CSE induced spontaneous apoptosis of human melanoma cells. The same effect was achieved using different H2 S donors, the most active of which was diallyl trisulfide (DATS). The main pro-apoptotic mechanisms involved were suppression of nuclear factor-κB activity and inhibition of AKT and extracellular signal-regulated kinase pathways. A proof of concept was obtained in vivo using a murine melanoma model. In fact, either l-cysteine, the CSE substrate, or DATS inhibited tumor growth in mice. In conclusion, we have determined that the l-cysteine/CSE/H2 S pathway is involved in melanoma progression.

  13. Progress and Promise of Genome-Wide Association Studies for Human Complex Trait Genetics

    PubMed Central

    Stranger, Barbara E.; Stahl, Eli A.; Raj, Towfique

    2011-01-01

    Enormous progress in mapping complex traits in humans has been made in the last 5 yr. There has been early success for prevalent diseases with complex phenotypes. These studies have demonstrated clearly that, while complex traits differ in their underlying genetic architectures, for many common disorders the predominant pattern is that of many loci, individually with small effects on phenotype. For some traits, loci of large effect have been identified. For almost all complex traits studied in humans, the sum of the identified genetic effects comprises only a portion, generally less than half, of the estimated trait heritability. A variety of hypotheses have been proposed to explain why this might be the case, including untested rare variants, and gene–gene and gene–environment interaction. Effort is currently being directed toward implementation of novel analytic approaches and testing rare variants for association with complex traits using imputed variants from the publicly available 1000 Genomes Project resequencing data and from direct resequencing of clinical samples. Through integration with annotations and functional genomic data as well as by in vitro and in vivo experimentation, mapping studies continue to characterize functional variants associated with complex traits and address fundamental issues such as epistasis and pleiotropy. This review focuses primarily on the ways in which genome-wide association studies (GWASs) have revolutionized the field of human quantitative genetics. PMID:21115973

  14. Recent progress in the discovery of natural inhibitors against human carboxylesterases.

    PubMed

    Wang, Dan-Dan; Zou, Li-Wei; Jin, Qiang; Hou, Jie; Ge, Guang-Bo; Yang, Ling

    2017-03-01

    Mammalian carboxylesterases (CEs) are important serine hydrolases catalyzing the hydrolysis of ester- or amide-containing compounds into the corresponding alcohols and carboxylic acids. In human, two primary carboxylesterases including hCE1 and hCE2 have been identified and extensively studied in the past decade. hCE1 is known to play crucial roles in the metabolism of a wide variety of endogenous esters, clinical drugs and insecticides, while hCE2 plays a key role in the metabolic activation of anticancer agents including irinotecan and capecitabine. The key roles of hCEs in both human health and xenobiotic metabolism arouse great interest in the discovery of potent and selective hCEs inhibitors to modulate endobiotic metabolism or to improve the outcomes of patients administrated with ester drugs. This review covers the significance and recent progress in the discovery of natural inhibitors against hCEs. The tools for screening and characterization of inhibitors against human CEs, including traditional LC-based approaches and the newly developed optical substrate-based assays, are summarized and discussed for the first time. Furthermore, the structural information and inhibitory capacities of all reported hCEs inhibitors including fatty acids, flavonoids, tanshinones and triterpenoids have been systematically summarized. All information and knowledge presented in this review will be very helpful for medicinal chemists to develop more potent and highly selective inhibitors against hCEs for potential biomedical applications.

  15. Human genetic marker for resistance to radiations and chemicals. 1998 annual progress report

    SciTech Connect

    Lieberman, H.B.

    1998-06-01

    'The broad objective of the project is to understand the molecular basis for the response of cells to radiations and chemicals, with the pragmatic goal of being able to identify human subpopulations that are exceptionally sensitive to DNA damaging agents. The project focuses on HRAD9, a human orthologue of the fission yeast Schizosaccharomyces pombe gene rad9. S. pombe rad9::ura4+ mutant cells are highly sensitive to ionizing radiation, UV and many chemicals, such as the DNA synthesis inhibitor hydroxyurea. They also lack the ability to delay cycling transiently in S phase or in G2 following a block in DNA replication or after incurring DNA damage, respectively -i.e., they lack checkpoint controls. The attempt by mutant cells to progress through mitosis in the absence of fully intact DNA accounts at least in part for their sensitivity to DNA damaging agents. Cells bearing rad9::ura4+ also aberrantly regulate UVDE, an enzyme that participates in a secondary DNA excision repair pathway. The key role played by S. pombe rad9 in promoting resistance to chemicals and radiations suggests that the evolutionarily conserved human cognate also has important functions in mammals. The first set of aims in this proposal centers on characterizing the structure and expression of HRAD9, to assess structure/function relationships and potentially link protein activity to a specific tissue. The next set of aims focuses on determining the role of HRAD9 in radio/chemoresponsiveness and cancer.'

  16. Murine Ccl2/Cx3cr1 Deficiency Results in Retinal Lesions Mimicking Human Age-Related Macular Degeneration

    PubMed Central

    Tuo, Jingsheng; Bojanowski, Christine M.; Zhou, Min; Shen, Defen; Ross, Robert J.; Rosenberg, Kevin I.; Cameron, D. Joshua; Yin, Chunyue; Kowalak, Jeffrey A.; Zhuang, Zhengping; Zhang, Kang; Chan, Chi-Chao

    2007-01-01

    Purpose Senescent Ccl2-/- mice are reported to develop cardinal features of human age-related macular degeneration (AMD). Loss-of-function single-nucleotide polymorphisms within CX3CR1 are also found to be associated with AMD. The authors generated Ccl2-/-/Cx3cr1-/- mice to establish a more characteristic and reproducible AMD model. Methods Single Ccl2- and Cx3cr1-deficient mice were crossbred to obtain Ccl2-/-/Cx3cr1-/- mice. Funduscopy, histopathology, retinal A2E quantification, proteomics, RT-PCR gene expression assay, immunochemistry, and Western blotting were used to examine the retina and to evaluate gene expression within the retinal tissue. Results By 6 weeks of age, all Ccl2-/-/Cx3cr1-/- mice developed AMD-like retinal lesions, including drusen, retinal pigment epithelium alteration, and photoreceptor degeneration. Furthermore, choroidal neovascularization occurred in 15% of the mice. These degenerative lesions progressed with age. A2E, a major lipofuscin fluorophore that accumulated during AMD progression, was significantly higher in the Ccl2-/-/Cx3cr1-/- retina than in the wild-type retina. Complement cofactor was higher in the Ccl2-/-/Cx3cr1-/- RPE. Proteomics data indicated that four proteins were differentially expressed in Ccl2-/-/Cx3cr1-/- retina compared with control. One of these proteins, ERp29, an endoplasmic reticulum protein, functions as an escort chaperone and in protein folding. Conclusions The authors concluded that Ccl2-/-/Cx3cr1-/- mice develop a broad spectrum of AMD abnormalities with early onset and high penetrance. These observations implicate certain chemokines and endoplasmic reticulum proteins in AMD pathogenesis. Similar to the mechanism of neurodegeneration caused by dysfunction of endoplasmic reticulum proteins, decreased chaperoning may cause misfolded protein accumulation, leading to drusen formation and retinal degeneration. PMID:17652758

  17. Genetic and Developmental Perspective of Language Abnormality in Autism and Schizophrenia: One Disease Occurring at Different Ages in Humans?

    PubMed

    Wang, Haoran George; Jeffries, Joseph Joel; Wang, Tianren Frank

    2016-04-01

    Language and communication through it are two of the defining features of normally developed human beings. However, both these functions are often impaired in autism and schizophrenia. In the former disorder, the problem usually emerges in early childhood (~2 years old) and typically includes a lack of communication. In the latter condition, the language problems usually occur in adolescence and adulthood and presents as disorganized speech. What are the fundamental mechanisms underlying these two disorders? Is there a shared genetic basis? Are the traditional beliefs about them true? Are there any common strategies for their prevention and management? To answer these questions, we searched PubMed by using autism, schizophrenia, gene, and language abnormality as keywords, and we reconsidered the basic concepts about these two diseases or syndromes. We found many functional genes, for example, FOXP2, COMT, GABRB3, and DISC1, are actually implicated in both of them. After observing the symptoms, genetic correlates, and temporal progression of these two disorders as well as their relationships more carefully, we now infer that the occurrence of these two diseases is likely developmentally regulated via interaction between the genome and the environment. Furthermore, we propose a unified view of autism and schizophrenia: a single age-dependently occurred disease that is newly named as Systemic Integral Disorder: if occurring in children before age 2, it is called autism; if in adolescence or a later age, it is called schizophrenia.

  18. Effects of age-associated regional changes in aortic stiffness on human hemodynamics revealed by computational modeling

    PubMed Central

    Cuomo, Federica; Roccabianca, Sara; Dillon-Murphy, Desmond; Xiao, Nan; Humphrey, Jay D.

    2017-01-01

    Although considered by many as the gold standard clinical measure of arterial stiffness, carotid-to-femoral pulse wave velocity (cf-PWV) averages material and geometric properties over a large portion of the central arterial tree. Given that such properties may evolve differentially as a function of region in cases of hypertension and aging, among other conditions, there is a need to evaluate the potential utility of cf-PWV as an early diagnostic of progressive vascular stiffening. In this paper, we introduce a data-driven fluid-solid-interaction computational model of the human aorta to simulate effects of aging-related changes in regional wall properties (e.g., biaxial material stiffness and wall thickness) and conduit geometry (e.g., vessel caliber, length, and tortuosity) on several metrics of arterial stiffness, including distensibility, augmented pulse pressure, and cyclic changes in stored elastic energy. Using the best available biomechanical data, our results for PWV compare well to findings reported for large population studies while rendering a higher resolution description of evolving local and global metrics of aortic stiffening. Our results reveal similar spatio-temporal trends between stiffness and its surrogate metrics, except PWV, thus indicating a complex dependency of the latter on geometry. Lastly, our analysis highlights the importance of the tethering exerted by external tissues, which was iteratively estimated until hemodynamic simulations recovered typical values of tissue properties, pulse pressure, and PWV for each age group. PMID:28253335

  19. How individual age-associated changes may influence human morbidity and mortality patterns.

    PubMed

    Ukraintseva, S V; Yashin, A I

    2001-09-15

    Patterns of human mortality share common traits in different populations. They include higher mortality in early childhood, lower mortality during the reproductive period, an accelerated increase of mortality near the end of the reproductive period, and deceleration in the mortality increase at oldest old ages. The deceleration of mortality rate is one of the most intriguing recent findings in longevity research. The role of differential selection in this phenomenon has been well studied. Possible contribution of individual aging in the shape of mortality curve is also recognized. However, this contribution has not been studied in details. In this paper, we specify most common patterns of age-associated changes in an individual organism and discuss their possible influence on morbidity and mortality in population. We subdivide individual age-associated changes into three components, having different influence on morbidity and mortality: (1) basal, (2) ontogenetic, and (3) time-dependent. Basal changes are connected with the universal decrease in the rate of living during an individual life. As a result, some phenotypic effects of aging may accumulate in an organism at a slower rate with age. Basal changes are likely to contribute to a plateau of morbidity often observed at old ages, and may partially be responsible for mortality deceleration at oldest old ages. Ontogenetic component is connected with change of the stages of ontogenesis (e.g., the growth, the reproductive period and the climacteric) during an individual life. The ontogenesis-related changes contribute to wave-like patterns of morbidity in population and may partially be responsible for mortality increase at middle ages and its deceleration at old ages. Time-dependent changes are connected with long-time exposure of an organism to different harmful factors. They are most likely to contribute to morbidity and mortality acceleration. We discuss how all three components of individual age

  20. Developing Humanities Collections in the Digital Age: Exploring Humanities Faculty Engagement with Electronic and Print Resources

    ERIC Educational Resources Information Center

    Kachaluba, Sarah Buck; Brady, Jessica Evans; Critten, Jessica

    2014-01-01

    This article is based on quantitative and qualitative research examining humanities scholars' understandings of the advantages and disadvantages of print versus electronic information resources. It explores how humanities' faculty members at Florida State University (FSU) use print and electronic resources, as well as how they perceive these…

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

    PubMed

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

    1997-11-01

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

  2. Radiodensity and hardness of enamel and dentin of human and bovine teeth, varying bovine teeth age.

    PubMed

    Fonseca, R B; Haiter-Neto, F; Carlo, H L; Soares, C J; Sinhoreti, M A C; Puppin-Rontani, R M; Correr-Sobrinho, L

    2008-11-01

    Studies have evaluated dental hard tissues characteristics from animal species in order to be used as a substitute for human teeth. The aim of this study was to evaluate the radiodensity and hardness of human and bovine enamel and dentin, varying bovine teeth age. Five specimens (1mm thick) were obtained from animals aged 20 (B20), 30 (B30), 38 (B38) and 48 (B48)months and from 20 to 30-years-old human third molars (H). The radiographic images were taken with a phosphor plaque digital system (Digora Optime). The radiodensity was obtained and Knoop hardness (KHN) was recorded (100g for 15s--5 indentations per specimen). Data were analyzed by one-way ANOVA following Tukey's HSD test and Dunnet's two-sided t-test. Radiodensity was similar within enamel groups, but bovine dentin presented higher radiodensity than human one regardless of age groups. Enamel-KHN showed differences between B20-B30 and B38-B48-H, and dentin-KHN was similar within all groups. Enamel was always more radiodense than dentin and also presented higher KHN (p=0.001). The use of bovine enamel or dentin should take into consideration the teeth age, but as a general rule it should be recommended to select older bovine teeth due to better chances to find greater similarity with human teeth.

  3. Ultrastructural age-related changes in the sensory corpuscles of the human genital skin.

    PubMed

    Tammaro, A; Parisella, F R; Cavallotti, C; Persechino, S; Cavallotti, C

    2013-01-01

    In human genital skin the majority of superficial sensory corpuscles is represented by glomerular corpuscles. These corpuscles show an own morphology. Our aim is to compare the ultra-structure of superficial sensory corpuscles in the penis skin of younger and older subjects. In this report the ultra-structure of the sensitive corpuscle in the penis skin of the younger and older subjects was compared, showing that the genital skin of the older humans contains more simple complexes than the younger ones. Our findings support the view that the age-related changes that can be observed in human glomerular genital corpuscles are consistent with an increase of the simple complexes and a strong decrease of the poly-lamellar one in the older people. These findings demonstrate that human genital corpuscles underwent age-related changes. Moreover our morphological findings can be correlated in relation to the clinical evolution of the sensitivity in the genital skin.

  4. CD99 polymorphisms significantly influence the probability to develop Ewing sarcoma in earlier age and patient disease progression

    PubMed Central

    Martinelli, Marcella; Parra, Alessandro; Scapoli, Luca; Sanctis, Paola De; Chiadini, Valentina; Hattinger, Claudia; Picci, Piero

    2016-01-01

    Ewing sarcoma (EWS), the second most common primary bone tumor in pediatric age, is known for its paucity of recurrent somatic abnormalities. Apart from the chimeric oncoprotein that derives from the fusion of EWS and FLI genes, recent genome-wide association studies have identified susceptibility variants near the EGR2 gene that regulate DNA binding of EWS-FLI. However, to induce transformation, EWS-FLI requires the presence of additional molecular events, including the expression of CD99, a cell surface molecule with critical relevance for the pathogenesis of EWS. High expression of CD99 is a common and distinctive feature of EWS cells, and it has largely been used for the differential diagnosis of the disease. The present study first links CD99 germline genetic variants to the susceptibility of EWS development and its progression. In particular, a panel of 25 single nucleotide polymorphisms has been genotyped in a case-control study. The CD99 rs311059 T variant was found to be significantly associated [P value = 0.0029; ORhet = 3.9 (95% CI 1.5-9.8) and ORhom = 5.3 (95% CI 1.2-23.7)] with EWS onset in patients less than 14 years old, while the CD99 rs312257-T was observed to be associated [P value = 0.0265; ORhet = 3.5 (95% CI 1.3-9.9)] with a reduced risk of relapse. Besides confirming the importance of CD99, our findings indicate that polymorphic variations in this gene may affect either development or progression of EWS, leading to further understanding of this cancer and development of better diagnostics/prognostics for children and adolescents with this devastating disease. PMID:27792997

  5. Comparison of oxime reactivation and aging of nerve agent-inhibited monkey and human acetylcholinesterases.

    PubMed

    Luo, Chunyuan; Tong, Min; Maxwell, Donald M; Saxena, Ashima

    2008-09-25

    Non-human primates are valuable animal models that are used for the evaluation of nerve agent toxicity as well as antidotes and results from animal experiments are extrapolated to humans. It has been demonstrated that the efficacy of an oxime primarily depends on its ability to reactivate nerve agent-inhibited acetylcholinesterase (AChE). If the in vitro oxime reactivation of nerve agent-inhibited animal AChE is similar to that of human AChE, it is likely that the results of an in vivo animal study will reliably extrapolate to humans. Therefore, the goal of this study was to compare the aging and reactivation of human and different monkey (Rhesus, Cynomolgus, and African Green) AChEs inhibited by GF, GD, and VR. The oximes examined include the traditional oxime 2-PAM, two H-oximes HI-6 and HLo-7, and the new candidate oxime MMB4. Results indicate that oxime reactivation of all three monkey AChEs was very similar to human AChE. The maximum difference in the second-order reactivation rate constant between human and three monkey AChEs or between AChEs from different monkey species was 5-fold. Aging rate constants of GF-, GD-, and VR-inhibited monkey AChEs were very similar to human AChE except for GF-inhibited monkey AChEs, which aged 2-3 times faster than the human enzyme. The results of this study suggest that all three monkey species are suitable animal models for nerve agent antidote evaluation since monkey AChEs possess similar biochemical/pharmacological properties to human AChE.

  6. Progressive human immunodeficiency virus-associated vasculopathy: time to revise antiretroviral therapy guidelines?

    PubMed

    Ntusi, N B A; Taylor, D; Naidoo, N G; Mendelson, M

    2011-01-01

    Cardiovascular abnormalities were appreciated early in the epidemic of the acquired immunodeficiency syndrome (AIDS), even before the aetiological agent, human immunodeficiency virus (HIV) was isolated and characterised. The aetiology and pathogenesis of cardiovascular disease in HIV infection is still the subject of intense speculation, and is likely multi-factorial. HIV affects every aspect of the cardiac axis, causing pericarditis, myocarditis, cardiomyopathy, coronary artery disease and microvascular dysfunction, valvular heart disease, pulmonary vascular disease and pulmonary hypertension, stroke and peripheral vascular disease. HIV-associated vasculopathy is an increasingly recognised clinical entity, causing high morbidity and increasing mortality in southern Africa, particularly from stroke and cardiovascular disease. HIV causes disease of the vascular tree, either by a direct effect on vascular or perivascular tissue, or indirectly via immune complex-mediated mechanisms, associated opportunistic infections and malignancies. As a result, highly active antiretroviral therapy (HAART) may have an important role in controlling disease progression. We report a case of histologically defined primary HIV vasculopathy in which the chance to start HAART was initially missed and in which the patient progressed to require bilateral amputations, but obtained disease quiescence upon commencement of HAART.

  7. The Neurotensin Receptor-1 Pathway Contributes to Human Ductal Breast Cancer Progression

    PubMed Central

    Dupouy, Sandra; Viardot-Foucault, Véronique; Alifano, Marco; Souazé, Frédérique; Plu-Bureau, Geneviève; Chaouat, Marc; Lavaur, Anne; Hugol, Danielle; Gespach, Christian

    2009-01-01

    Background The neurotensin (NTS) and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1), are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion. Methods and Results we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs) by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. Conclusion these data support the activation of neurotensinergic deleterious pathways in breast cancer progression. PMID:19156213

  8. Dysregulation of JAM-A plays an important role in human tumor progression.

    PubMed

    Zhao, Chen; Lu, Funian; Chen, Hongxia; Zhao, Xianda; Sun, Jun; Chen, Honglei

    2014-01-01

    Junctional adhesion molecule A (JAM-A) is a transmembrane protein that belongs to the immunoglobulin (Ig) superfamily. Evidence determines that JAM-A plays a role in numerous cellular processes, including tight junction assembly, leukocyte migration, platelet activation, angiogenesis and virus binding. Recent research suggests that JAM-A is dysregulated in various cancers and is vital for tumor progression. JAM-A is implicated in carcinogenesis via different signal pathways such as TGF-β1 signaling. Furthermore, JAM-A expression in cancers is usually associated with certain outcome of patients and might be a prognostic indicator. In this review, the correlation between JAM-A expression and human cancers will be described.

  9. Progress toward implementation of human papillomavirus vaccination--the Americas, 2006-2010.

    PubMed

    2011-10-14

    Cervical cancer is a major cause of morbidity and mortality in the Americas, where an estimated 80,574 new cases and 36,058 deaths were reported in 2008, with 85% of this burden occurring in Latin America and the Caribbean. Two oncogenic human papillomavirus (HPV) types (16 and 18) cause approximately 70% of cervical cancers and a substantial proportion of other HPV-related cancers. HPV vaccination provides an opportunity to greatly reduce cervical cancer burden through primary prevention of HPV infection. This report summarizes the progress toward HPV vaccine introduction in the Americas, focusing on countries that have introduced the vaccine in national or regional immunization programs. As of January 2011, four countries in the Americas had introduced HPV vaccine. Overcoming issues related to financing and delivery of HPV vaccine remains a key public health challenge to more widespread implementation of HPV vaccination in the Americas.

  10. Cell cycle progression and de novo centriole assembly after centrosomal removal in untransformed human cells

    PubMed Central

    Uetake, Yumi; Lončarek, Jadranka; Nordberg, Joshua J.; English, Christopher N.; La Terra, Sabrina; Khodjakov, Alexey; Sluder, Greenfield

    2007-01-01

    How centrosome removal or perturbations of centrosomal proteins leads to G1 arrest in untransformed mammalian cells has been a mystery. We use microsurgery and laser ablation to remove the centrosome from two types of normal human cells. First, we find that the cells assemble centrioles de novo after centrosome removal; thus, this phenomenon is not restricted to transformed cells. Second, normal cells can progress through G1 in its entirety without centrioles. Therefore, the centrosome is not a necessary, integral part of the mechanisms that drive the cell cycle through G1 into S phase. Third, we provide evidence that centrosome loss is, functionally, a stress that can act additively with other stresses to arrest cells in G1 in a p38-dependent fashion. PMID:17227892

  11. Positron emission tomography and computed tomography assessments of the aging human brain

    SciTech Connect

    de Leon, M.J.; George, A.E.; Ferris, S.H.; Christman, D.R.; Fowler, J.S.; Gentes, C.I.; Brodie, J.; Reisberg, B.; Wolf, A.P.

    1984-02-01

    The relationship between alterations in brain structure and brain function was studied in vivo in both young and elderly human subjects. Computed tomography revealed significant age-related ventricular and cortical sulcal dilatation. The cortical changes were most closely related to age. Positron emission tomography failed to show regional changes in brain glucose metabolic rate. The results suggest that the normal aging brain undergoes structural atrophic changes without incurring regional metabolic changes. Examination of the correlations between the structural and the metabolic measures revealed no significant relationships. These data are discussed with respect to the significant structure-function relationships that have been reported in Alzheimer disease. 27 references, 3 figures, 2 tables.

  12. Chronic Alcohol Abuse and HIV Disease Progression: Studies with the Non-Human Primate Model

    PubMed Central

    Amedee, Angela M.; Nichols, Whitney A.; Robichaux, Spencer; Bagby, Gregory J.; Nelson, Steve

    2015-01-01

    The populations at risk for HIV infection, as well as those living with HIV, overlap with populations that engage in heavy alcohol consumption. Alcohol use has been associated with high-risk sexual behavior and an increased likelihood of acquiring HIV, as well as poor outcome measures of disease such as increased viral loads and declines in CD4+ T lymphocytes among those living with HIV-infections. It is difficult to discern the biological mechanisms by which alcohol use affects the virus:host interaction in human populations due to the numerous variables introduced by human behavior. The rhesus macaque infected with simian immunodeficiency virus has served as an invaluable model for understanding HIV disease and transmission, and thus, provides an ideal model to evaluate the effects of chronic alcohol use on viral infection and disease progression in a controlled environment. In this review, we describe the different macaque models of chronic alcohol consumption and summarize the studies conducted with SIV and alcohol. Collectively, they have shown that chronic alcohol consumption results in higher levels of plasma virus and alterations in immune cell populations that potentiate SIV replication. They also demonstrate a significant impact of chronic alcohol use on SIV-disease progression and survival. These studies highlight the utility of the rhesus macaque in deciphering the biological effects of alcohol on HIV disease. Future studies with this well-established model will address the biological influence of alcohol use on susceptibility to HIV, as well as the efficacy of anti-retroviral therapy. PMID:25053367

  13. An Improved Syngeneic Orthotopic Murine Model of Human Breast Cancer Progression

    PubMed Central

    Rashid, Omar M.; Nagahashi, Masayuki; Ramachandran, Suburamaniam; Dumur, Catherine; Schaum, Julia; Yamada, Akimitsu; Terracina, Krista P.; Milstien, Sheldon; Spiegel, Sarah; Takabe, Kazuaki

    2014-01-01

    Purpose Breast cancer drug development costs nearly $610 million and 37 months in preclinical mouse model trials with minimal success rates. Despite these inefficiencies, there are still no consensus breast cancer preclinical models. Methods Murine mammary adenocarcinoma 4T1-luc2 cells were implanted subcutaneous (SQ) or orthotopically percutaneous injection in the area of the nipple (OP), or surgically into the chest 2nd mammary fat pad under direct vision (ODV) in Balb/c immunocompetent mice. Tumor progression was followed by in vivo bioluminescence and direct measurements, pathology and survival determined, and tumor gene expression analyzed by genome-wide microarrays. Results ODV produced less variable sized tumors and was a reliable method of implantation. ODV implantation into the chest 2nd mammary pad rather than into the abdominal 4th mammary pad, the most common implantation site, better mimicked human breast cancer progression pattern, which correlated with bioluminescent tumor burden and survival. Compared to SQ, ODV produced tumors that differentially expressed genes whose interaction networks are of importance in cancer research. qPCR validation of 10 specific target genes of interest in ongoing clinical trials demonstrated significant differences in expression. Conclusions ODV implantation into the chest 2nd mammary pad provides the most reliable model that mimics human breast cancer compared from subcutaneous implantation that produces tumors with different genome expression profiles of clinical significance. Increased understanding of the limitations of the different preclinical models in use will help guide new investigations and may improve the efficiency of breast cancer drug development. PMID:25200444

  14. Age-related changes in human posture control: Motor coordination tests

    NASA Technical Reports Server (NTRS)

    Peterka, R. J.; Black, F. O.

    1989-01-01

    Postural responses to support surface displacements were measured in 214 normal human subjects ranging in age from 7 to 81 years. Motor tests measured leg muscle Electromyography (EMG) latencies, body sway, and the amplitude and timing of changes in center of pressure displacements in response to sudden forward and backward horizontal translations of the support surface upon which the subjects stood. There were small increases in both EMG latencies and the time to reach the peak amplitude of center of pressure responses with increasing age. The amplitude of center of pressure responses showed little change with age if the amplitude measures were normalized by a factor related to subject height. In general, postural responses to sudden translations showed minimal changes with age, and all age related trends which were identified were small relative to the variability within the population.

  15. An analysis of human skeletal remains with cerebral palsy: associated skeletal age delay and dental pathologies.

    PubMed

    Megyesi, Mary S; Tubbs, Ryan M; Sauer, Norman J

    2009-03-01

    In 2002 the authors were asked to examine the skeletal remains of an individual with a known history of severe cerebral palsy (CP) who was 21-23 years old at death. Skeletal age estimates of 11-15 years and dental age estimates of c. 16 years are younger than the known age of the decedent. Skeletal analysis also identified dental pathologies such as chronic tooth grinding and substantial calculus deposits. Scarce literature exists on forensic human remains cases with CP, and this study contrasts the age discrepancy and other features of this case with typical clinical characteristics of CP. A review of the CP literature suggests that delayed skeletal maturation and dental pathologies such as those observed in this case are indicative of complications related to CP. This article may alert future investigators to some of the osteological signs of CP and the probability that age indicators may be misleading.

  16. Regulation of skeletal muscle blood flow during exercise in ageing humans.

    PubMed

    Hearon, Christopher M; Dinenno, Frank A

    2016-04-15

    The regulation of skeletal muscle blood flow and oxygen delivery to contracting skeletal muscle is complex and involves the mechanical effects of muscle contraction; local metabolic, red blood cell and endothelium-derived substances; and the sympathetic nervous system (SNS). With advancing age in humans, skeletal muscle blood flow is typically reduced during dynamic exercise and this is due to a lower vascular conductance, which could ultimately contribute to age-associated reductions in aerobic exercise capacity, a primary predictor of mortality in both healthy and diseased ageing populations. Recent findings have highlighted the contribution of endothelium-derived substances to blood flow control in contracting muscle of older adults. With advancing age, impaired nitric oxide availability due to scavenging by reactive oxygen species, in conjunction with elevated vasoconstrictor signalling via endothelin-1, reduces the local vasodilatory response to muscle contraction. Additionally, ageing impairs the ability of contracting skeletal muscle to blunt sympathetic vasoconstriction (i.e. 'functional sympatholysis'), which is critical for the proper regulation of tissue blood flow distribution and oxygen delivery, and could further reduce skeletal muscle perfusion during high intensity and/or large muscle mass exercise in older adults. We propose that initiation of endothelium-dependent hyperpolarization is the underlying signalling event necessary to properly modulate sympathetic vasoconstriction in contracting muscle, and that age-associated impairments in red blood cell adenosine triphosphate release and stimulation of endothelium-dependent vasodilatation may explain impairments in both local vasodilatation and functional sympatholysis with advancing age in humans.

  17. New phytochemicals as potential human anti-aging compounds: Reality, promise, and challenges.

    PubMed

    Corrêa, Rubia C G; Peralta, Rosane M; Haminiuk, Charles W I; Maciel, Giselle Maria; Bracht, Adelar; Ferreira, Isabel C F R

    2016-09-13

    Aging is an inevitable process influenced by genetic, lifestyle and environmental factors. Indirect evidence shows that several phytochemicals can have anti-aging capabilities, although direct evidence in this field is still limited. This report aims to provide a critical review on aspects related to the use of novel phytochemicals as anti-aging agents, to discuss the obstacles found when performing most anti-aging study protocols in humans, and to analyze future perspectives. In addition to the extensively studied resveratrol, epicatechin, quercetin and curcumin, new phytochemicals have been reported to act as anti-aging agents, such as the amino acid L-theanine isolated from green tea, and the lignans arctigenin and matairesinol isolated from Arctium lappa seeds. Furthermore, this review discusses the application of several new extracts rich in phytochemicals with potential use in anti aging therapies. Finally, this review also discusses the most important biomarkers to test anti-aging interventions, the necessity of conducting epidemiological studies and the need of clinical trials with adequate study protocols for humans.

  18. Human Age Estimation Method Robust to Camera Sensor and/or Face Movement

    PubMed Central

    Nguyen, Dat Tien; Cho, So Ra; Pham, Tuyen Danh; Park, Kang Ryoung

    2015-01-01

    Human age can be employed in many useful real-life applications, such as customer service systems, automatic vending machines, entertainment, etc. In order to obtain age information, image-based age estimation systems have been developed using information from the human face. However, limitations exist for current age estimation systems because of the various factors of camera motion and optical blurring, facial expressions, gender, etc. Motion blurring can usually be presented on face images by the movement of the camera sensor and/or the movement of the face during image acquisition. Therefore, the facial feature in captured images can be transformed according to the amount of motion, which causes performance degradation of age estimation systems. In this paper, the problem caused by motion blurring is addressed and its solution is proposed in order to make age estimation systems robust to the effects of motion blurring. Experiment results show that our method is more efficient for enhancing age estimation performance compared with systems that do not employ our method. PMID:26334282

  19. NF-κB and Androgen Receptor Variant Expression Correlate with Human BPH progression

    PubMed Central

    Austin, David C; Strand, Douglas W; Love, Harold L; Franco, Omar E; Jang, Alex; Grabowska, Magdalena M; Miller, Nicole L; Hameed, Omar; Clark, Peter E; Fowke, Jay H; Matusik, Robert J; Jin, Ren J; Hayward, Simon W

    2016-01-01

    Background Benign prostatic hyperplasia (BPH) is a common, chronic progressive disease. Inflammation is associated with prostatic enlargement and resistance to 5α-reductase inhibitor (5ARI) therapy. Activation of the nuclear factor-kappa B (NF-κB) pathway is linked to both inflammation and ligand-independent prostate cancer progression. Methods NF-κB activation and androgen receptor variant (AR-V) expression were quantified in transition zone tissue samples from patients with a wide range of AUASS from incidental BPH in patients treated for low grade, localized peripheral zone prostate cancer to advanced disease requiring surgical intervention. To further investigate these pathways, human prostatic stromal and epithelial cell lines were transduced with constitutively active or kinase dead forms of IKK2 to regulate canonical NF-κB activity. The effects on AR full length (AR-FL) and androgen-independent AR-V expression as well as cellular growth and differentiation were assessed. Results Canonical NF-κB signaling was found to be upregulated in late versus early stage BPH, and to be strongly associated with non-insulin dependent diabetes mellitus. Elevated expression of AR-variant 7 (AR-V7), but not other AR variants, was found in advanced BPH samples. Expression of AR-V7 significantly correlated with the patient AUASS and TRUS volume. Forced activation of canonical NF-κB in human prostatic epithelial and stromal cells resulted in elevated expression of both AR-FL and AR-V7, with concomitant ligand-independent activation of AR reporters. Activation of NF-κB and over expression of AR-V7 in human prostatic epithelial cells maintained cell viability in the face of 5ARI treatment. Conclusion Activation of NF-κB and AR-V7 in the prostate is associated with increased disease severity. AR-V7 expression is inducible in human prostate cells by forced activation of NF-κB resulting in resistance to 5ARI treatment, suggesting a potential mechanism by which patients may

  20. Urine proteomes of healthy aging humans reveal extracellular matrix (ECM) alterations and immune system dysfunction.

    PubMed

    Bakun, M; Senatorski, G; Rubel, T; Lukasik, A; Zielenkiewicz, P; Dadlez, M; Paczek, L

    2014-02-01

    Aging is a complex physiological process that poses considerable conundrums to rapidly aging societies. For example, the risk of dying from cardiovascular diseases and/or cancer steadily declines for people after their 60s, and other causes of death predominate for seniors older than 80 years of age. Thus, physiological aging presents numerous unanswered questions, particularly with regard to changing metabolic patterns. Urine proteomics analysis is becoming a non-invasive and reproducible diagnostic method. We investigated the urine proteomes in healthy elderly people to determine which metabolic processes were weakened or strengthened in aging humans. Urine samples from 37 healthy volunteers aged 19-90 years (19 men, 18 women) were analyzed for protein expression by liquid chromatography-tandem mass spectrometry. This generated a list of 19 proteins that were differentially expressed in different age groups (young, intermediate, and old age). In particular, the oldest group showed protein changes reflective of altered extracellular matrix turnover and declining immune function, in which changes corresponded to reported changes in cardiovascular tissue remodeling and immune disorders in the elderly. Thus, urinary proteome changes in the elderly appear to reflect the physiological processes of aging and are particularly clearly represented in the circulatory and immune systems. Detailed identification of "protein trails" creates a more global picture of metabolic changes that occur in the elderly.

  1. Morphometric analysis of arteriolar tortuosity in human cerebral white matter of preterm, young, and aged subjects.

    PubMed

    Thore, Clara R; Anstrom, John A; Moody, Dixon M; Challa, Venkata R; Marion, Miranda C; Brown, William R

    2007-05-01

    Arteriolar tortuousities, consisting of vascular coils, loops, and spirals, appear in white matter in a subset of human cerebral vessels. Computerized morphometry was used to analyze brain sections from a broad age range of subjects to determine whether tortuosity is a phenomenon of aging or is associated with leukoaraiosis (LA) or Alzheimer disease (AD). Autopsy brains were studied from 55 subjects ranging in age from 23 weeks postconception to 102 years. Fourteen aged subjects were diagnosed with LA and 7 with AD. By using computerized morphometry, vascular curl (curvilinear length/straight length) was measured in white matter arterioles in 100-microm-thick, alkaline phosphatase-stained sections. Aging subjects, compared with young subjects, showed significant increases in both the prevalence and severity of tortuosity. Curl scores in aged subjects with LA or AD were not significantly different from aged controls without LA or AD. We conclude that 1) tortuous vessels are extremely rare in preterm babies, children, or young adults; 2) significant tortuosity, as indicated by elevated curl scores, begins in middle age; 3) tortuosity does not appear in a subset of aged individuals regardless of longevity; and 4) tortuosity does not appear in a subset of individuals with either LA or AD.

  2. In vivo quantification of human dermal skin aging using SHG and autofluorescence

    NASA Astrophysics Data System (ADS)

    Puschmann, Stefan; Rahn, Christian-Dennis; Wenck, Horst; Gallinat, Stefan; Fischer, Frank

    2012-03-01

    There are visible changes during skin aging. In the extracellular matrix these changes referred to as intrinsic aging (skin areas not exposed to sunlight) and extrinsic aging can be measured using various methods, such as subjective clinical evaluation, histology and molecular analysis. In this study we developed a new parameter for the non-invasive quantitative determination of dermal skin aging utilizing a five-dimensional intravital tomography (5D-IVT). This device, also known as 5D - multi-photon laser scanning microscopy, is a powerful tool to investigate (photo)aging-associated alterations in vivo. Structural alterations in the dermis of extrinsically aged (chronically sun-exposed) and intrinsically aged (sun-protected) human skin were recorded utilizing the collagen-specific second harmonic generation (SHG) signal and the elastin-specific autofluorescence (AF) signal. Recording took place in young and elderly volunteers. The resulting images were processed in order to gain the elastin percentage and the collagen percentage per image. Then, the elastin - to - collagen ratio (ELCOR) was calculated. With respect to volar forearm skin, the ELCOR significantly increased with age. In elderly volunteers, the ELCOR value calculated for the chronically sun-exposed temple area was significantly augmented compared with the sun-protected upper arm area. Based on 5D-IVT we introduce the ELCOR as a new means to quantify age-associated alterations in the extracellular matrix of in vivo human skin. This novel parameter is compared to the currently used "SHG to AF aging index" of the dermis (SAAID).

  3. [Dietary habits and the state of the human oral cavity in the prehistoric age].

    PubMed

    Kee, C D

    1990-06-01

    This is an age-by-age summation of literature on over 100 sites (of more than 250 excavated prehistoric ruins on the Korean Peninsula: about 160 places in South Korea--Paleolithic Age 15, Neolithic Age 21, Bronze Age 90 and Iron Age 35--and about 90 places in North Korea) which produced dietary-habit-related devices such as hunting tools, fishing instruments, farming equipments, tools of daily life, and human bones and teeth. 1) Various dietary-habit-related Old Stone-Age tools, instruments and other items were found. Among them were stone axes, stone hand axes, fish spears and hooks made of bone or horn, stone blades, stone scrapers and stone drills believed to have been used in daily life, and charcoal and sites of furnaces used for cooking. Furthermore, it was found that there were severe dental abrasions and dental caries among the inhabitants of the Korean Peninsula in the Old Stone Age. 2) Some evidences were found which lead us to believe that hunting was practiced with stone arrowheads in the New Stone Age. Stone net sinkers, which is the evidence of the use of fish nets, were also found. In addition, farming stone tools and charred cereals, both of which date back to the latter part of this period, were unearthed. Millstones, which began to be used in this age, and livestock bones were found. Where these items were discovered, 23 maxillae and mandibles with teeth and a total of 231 separate teeth of Neolithic period human beings were reported. However, there are no records indicating dental caries, but some records describe severe abrasion.

  4. Erythrocyte membrane transporters during human ageing: modulatory role of tea catechins.

    PubMed

    Pandey, Kanti Bhooshan; Jha, Rashmi; Rizvi, Syed Ibrahim

    2013-02-01

    Ageing is associated with many physiological and cellular changes, many of which are due to alterations in the plasma membrane. The functions of membrane transporter proteins are crucial for the maintenance of ionic homeostasis between the extra- and intracellular environments. The aim of the present study was to determine the status of erythrocyte membrane transporters, specifically Ca(2+) -ATPases, Na(+) /K(+) -ATPases and the Na(+) /H(+) exchanger (NHE), during ageing in humans. Furthermore, because tea catechins have been reported to possess strong anti-oxidant potential, the study was extended to evaluate the effect of (-)-epicatechin (EC), (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin (EGC) and (-)-epigallocatechin-3-gallate (EGCG) on these transporters as a function of human age. The study was performed on 97 normal healthy subjects (62 men, 35 women; 16-80 years old). To investigate the effects of tea catechins, subjects were divided into three groups: young (<40 years old; n = 34); middle-aged (40-60 years old; n = 32); and old (>60 years old; n = 31). Erythrocyte ghosts/cell suspension from each group were incubated with ECG, EGCG, EGC and EC (10 μmol/L) for 30 min at 37°C prior to assay. Ageing significantly increased NHE activity and decreased Ca(2+) -ATPase activity. There were no significant changes in Na(+) /K(+) -ATPase activity during the ageing process. (-)-Epigallocatechin-3-gallate, EGC, ECG and EC effectively mitigated the changes in membrane transporter activity in erythrocytes from all age groups; however, the effect was more pronounced in the old age group. We hypothesize that impairment in -bound transporters may be one of the possible mechanisms underlying the pathological events during ageing. A higher intake of catechin-rich food may provide some protection against age-dependent diseases.

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

    PubMed Central

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

    2007-01-01

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

  6. Age-dependent changes in task-based modular organization of the human brain.

    PubMed

    Schlesinger, Kimberly J; Turner, Benjamin O; Lopez, Brian A; Miller, Michael B; Carlson, Jean M

    2017-02-01

    As humans age, cognition and behavior change significantly, along with associated brain function and organization. Aging has been shown to decrease variability in functional magnetic resonance imaging (fMRI) signals, and to affect the modular organization of human brain function. In this work, we use complex network analysis to investigate the dynamic community structure of large-scale brain function, asking how evolving communities interact with known brain systems, and how the dynamics of communities and brain systems are affected by age. We analyze dynamic networks derived from fMRI scans of 104 human subjects performing a word memory task, and determine the time-evolving modular structure of these networks by maximizing the multislice modularity, thereby identifying distinct communities, or sets of brain regions with strong intra-set functional coherence. To understand how community structure changes over time, we examine the number of communities as well as the flexibility, or the likelihood that brain regions will switch between communities. We find a significant positive correlation between age and both these measures: younger subjects tend to have less fragmented and more coherent communities, and their brain regions tend to change communities less often during the memory task. We characterize the relationship of community structure to known brain systems by the recruitment coefficient, or the probability of a brain region being grouped in the same community as other regions in the same system. We find that regions associated with cingulo-opercular, somatosensory, ventral attention, and subcortical circuits have a significantly higher recruitment coefficient in younger subjects. This indicates that the within-system functional coherence of these specific systems during the memory task declines with age. Such a correspondence does not exist for other systems (e.g. visual and default mode), whose recruitment coefficients remain relatively uniform across ages

  7. A reverse genetics cell-based evaluation of genes linked to healthy human tissue age

    PubMed Central

    Crossland, Hannah; Atherton, Philip J.; Strömberg, Anna; Gustafsson, Thomas; Timmons, James A.

    2017-01-01

    We recently developed a binary (i.e., young vs. old) classifier using human muscle RNA profiles that accurately distinguished the age of multiple tissue types. Pathway analysis did not reveal regulators of these 150 genes, so we used reverse genetics and pharmacologic methods to explore regulation of gene expression. Using small interfering RNA, well-studied age-related factors (i.e., rapamycin, resveratrol, TNF-α, and staurosporine), quantitative real-time PCR and clustering analysis, we studied gene–gene interactions in human skeletal muscle and renal epithelial cells. Individual knockdown of 10 different age genes yielded a consistent pattern of gene expression in muscle and renal cells, similar to in vivo. Potential epigenetic interactions included HIST1H3E knockdown, leading to decreased PHF19 and PCDH9, and increased ICAM5 in muscle and renal cells, while ICAM5 knockdown reduced HIST1H3E expression. Resveratrol, staurosporine, and TNF-α significantly regulated the in vivo aging genes, while only rapamycin perturbed the healthy-age gene expression signature in a manner consistent with in vivo. In vitro coordination of gene expression for this in vivo tissue age signature indicates a degree of direct coordination, and the observed link with mTOR activity suggests a direct link between a robust biomarker of healthy neuromuscular age and a major axis of life span in model systems.—Crossland, H., Atherton, P. J., Strömberg, A., Gustafsson, T., Timmons, J. A. A reverse genetics cell-based evaluation of genes linked to healthy human tissue age. PMID:27698205

  8. The aging human cochlear nucleus: Changes in the glial fibrillary acidic protein, intracellular calcium regulatory proteins, GABA neurotransmitter and cholinergic receptor.

    PubMed

    Sharma, Saroj; Nag, Tapas C; Thakar, Alok; Bhardwaj, Daya N; Roy, Tara Sankar

    2014-03-01

    The human auditory system is highly susceptible to environmental and metabolic insults which further affect the biochemical and physiological milieu of the cells that may contribute to progressive, hearing loss with aging. The cochlear nucleus (CN) is populated by morphologically diverse types of neurons with discrete physiological and neurochemical properties. Between the dorsal and the ventral cochlear nucleus (DCN and VCN), the VCN is further sub-divided into the rostral (rVCN) and caudal (cVCN) sub-divisions. Although, information is available on the age related neurochemical changes in the mammalian CN similar reports on human CN is still sparse. The morphometry and semiquantitative analysis of intensity of expression of glial fibrillary acidic protein (GFAP), calcium binding proteins (calbindin, calretinin and parvalbumin), gamma amino butyric acid (GABA) and nicotinic acetyl choline receptor (nAchR) beta 2 immunostaining were carried out in all three sub-divisions of the human CN from birth to 90 years. There was increased GFAP immunoreactivity in decades 2 and 3 in comparison to decade 1 in the CN. But no change was observed in rVCN from decade 4 onwards, whereas intense staining was also observed in decades 5 and 6 in cVCN and DCN. All three calcium binding proteins were highly expressed in early to middle ages, whereas a significant reduction was found in later decades in the VCN. GABA and nAchR beta 2 expressions were unchanged throughout in all the decades. The middle age may represent a critical period of onset and progression of aging changes in the CN and these alterations may add to the deterioration of hearing responses in the old age.

  9. Human aneuploidy: mechanisms and new insights into an age-old problem

    PubMed Central

    Nagaoka, So I.; Hassold, Terry J.; Hunt, Patricia A.

    2012-01-01

    Trisomic and monosomic (aneuploid) embryos account for at least 10% of human pregnancies and, for women nearing the end of their reproductive lifespan, the incidence may exceed 50%. The errors that lead to aneuploidy almost always occur in the oocyte but, despite intensive investigation, the underlying molecular basis has remained elusive. Recent studies of humans and model organisms have shed new light on the complexity of meiotic defects, providing evidence that the age-related increase in errors in the human female is not attributable to a single factor but to an interplay between unique features of oogenesis and a host of endogenous and exogenous factors. PMID:22705668

  10. Coordinated Expression of Phosphoinositide Metabolic Genes during Development and Aging of Human Dorsolateral Prefrontal Cortex

    PubMed Central

    Rapoport, Stanley I.; Primiani, Christopher T.; Chen, Chuck T.; Ahn, Kwangmi; Ryan, Veronica H.

    2015-01-01

    Background Phosphoinositides, lipid-signaling molecules, participate in diverse brain processes within a wide metabolic cascade. Hypothesis Gene transcriptional networks coordinately regulate the phosphoinositide cascade during human brain Development and Aging. Methods We used the public BrainCloud database for human dorsolateral prefrontal cortex to examine age-related expression levels of 49 phosphoinositide metabolic genes during Development (0 to 20+ years) and Aging (21+ years). Results We identified three groups of partially overlapping genes in each of the two intervals, with similar intergroup correlations despite marked phenotypic differences between Aging and Development. In each interval, ITPKB, PLCD1, PIK3R3, ISYNA1, IMPA2, INPPL1, PI4KB, and AKT1 are in Group 1, PIK3CB, PTEN, PIK3CA, and IMPA1 in Group 2, and SACM1L, PI3KR4, INPP5A, SYNJ1, and PLCB1 in Group 3. Ten of the genes change expression nonlinearly during Development, suggesting involvement in rapidly changing neuronal, glial and myelination events. Correlated transcription for some gene pairs likely is facilitated by colocalization on the same chromosome band. Conclusions Stable coordinated gene transcriptional networks regulate brain phosphoinositide metabolic pathways during human Development and Aging. PMID:26168237

  11. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age

    PubMed Central

    2009-01-01

    Background In humans, the intestinal microbiota plays an important role in the maintenance of host health by providing energy, nutrients, and immunological protection. Applying current molecular methods is necessary to surmount the limitations of classical culturing techniques in order to obtain an accurate description of the microbiota composition. Results Here we report on the comparative assessment of human fecal microbiota from three age-groups: infants, adults and the elderly. We demonstrate that the human intestinal microbiota undergoes maturation from birth to adulthood and is further altered with ageing. The counts of major bacterial groups Clostridium leptum, Clostridium coccoides, Bacteroidetes, Bifidobacterium, Lactobacillus and Escherichia coli were assessed by quantitative PCR (qPCR). By comparing species diversity profiles, we observed age-related changes in the human fecal microbiota. The microbiota of infants was generally characterized by low levels of total bacteria. C. leptum and C. coccoides species were highly represented in the microbiota of infants, while elderly subjects exhibited high levels of E. coli and Bacteroidetes. We observed that the ratio of Firmicutes to Bacteroidetes evolves during different life stages. For infants, adults and elderly individuals we measured ratios of 0.4, 10.9 and 0.6, respectively. Conclusion In this work we have confirmed that qPCR is a powerful technique in studying the diverse and complex fecal microbiota. Our work demonstrates that the fecal microbiota composition evolves throughout life, from early childhood to old age. PMID:19508720

  12. Not so Big Communities: A Promising Future for Human Beings of All Ages

    ERIC Educational Resources Information Center

    Susanka, Sarah

    2011-01-01

    In many American communities today, the methods of construction, as well as the almost exclusive orientation to the convenience of the automobile, limit the functioning and independence of the aging population, and offer little opportunity for human interaction. Sarah Susanka's "Not So Big" series of books points toward a new way of…

  13. Individual Differences in Spatial Pattern Separation Performance Associated with Healthy Aging in Humans

    ERIC Educational Resources Information Center

    Stark, Shauna M.; Yassa, Michael A.; Stark, Craig E. L.

    2010-01-01

    Rodent studies have suggested that "pattern separation," the ability to distinguish among similar experiences, is diminished in a subset of aged rats. We extended these findings to the human using a task designed to assess spatial pattern separation behavior (determining at time of test whether pairs of pictures shown during the study were in the…

  14. History of the USDA Human Nutrition Research Center on Aging at Tufts University

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, while quite a mouthful, is aptly named, since it has contributed substantially to the legacy of Jean Mayer, to the scientific stature of the USDA and, in Atwater’s tradition, to the d...

  15. Rural origin, age, and endoparasite fecal prevalence in dogs surrendered to the Regina Humane Society, 2013

    PubMed Central

    Schurer, Janna M.; Hamblin, Brie; Davenport, Laura; Wagner, Brent; Jenkins, Emily J.

    2014-01-01

    We report the results of fecal parasite surveillance in dogs surrendered to the Regina Humane Society, Saskatchewan, Canada, between May and November 2013. Overall, 23% of 231 dogs were infected with at least 1 intestinal parasite. Endoparasite infection was positively associated with rural origin (P = 0.002) and age (< 12 months; P < 0.001). PMID:25477549

  16. Does Human Milk Modulate Body Composition in Late Preterm Infants at Term-Corrected Age?

    PubMed Central

    Giannì, Maria Lorella; Consonni, Dario; Liotto, Nadia; Roggero, Paola; Morlacchi, Laura; Piemontese, Pasqua; Menis, Camilla; Mosca, Fabio

    2016-01-01

    (1) Background: Late preterm infants account for the majority of preterm births and are at risk of altered body composition. Because body composition modulates later health outcomes and human milk is recommended as the normal method for infant feeding, we sought to investigate whether human milk feeding in early life can modulate body composition development in late preterm infants; (2) Methods: Neonatal, anthropometric and feeding data of 284 late preterm infants were collected. Body composition was evaluated at term-corrected age by air displacement plethysmography. The effect of human milk feeding on fat-free mass and fat mass content was evaluated using multiple linear regression analysis; (3) Results: Human milk was fed to 68% of the infants. According to multiple regression analysis, being fed any human milk at discharge and at  term-corrected and being fed exclusively human milk at term-corrected age were positively associated with fat-free mass content(β = −47.9, 95% confidence interval (CI) = −95.7; −0.18; p = 0.049; β = −89.6, 95% CI = −131.5; −47.7; p < 0.0001; β = −104.1, 95% CI = −151.4; −56.7, p < 0.0001); (4) Conclusion: Human milk feeding appears to be associated with fat-free mass deposition in late preterm infants. Healthcare professionals should direct efforts toward promoting and supporting breastfeeding in these vulnerable infants. PMID:27782098

  17. Does Human Milk Modulate Body Composition in Late Preterm Infants at Term-Corrected Age?

    PubMed

    Giannì, Maria Lorella; Consonni, Dario; Liotto, Nadia; Roggero, Paola; Morlacchi, Laura; Piemontese, Pasqua; Menis, Camilla; Mosca, Fabio

    2016-10-23

    (1) Background: Late preterm infants account for the majority of preterm births and are at risk of altered body composition. Because body composition modulates later health outcomes and human milk is recommended as the normal method for infant feeding, we sought to investigate whether human milk feeding in early life can modulate body composition development in late preterm infants; (2) Methods: Neonatal, anthropometric and feeding data of 284 late preterm infants were collected. Body composition was evaluated at term-corrected age by air displacement plethysmography. The effect of human milk feeding on fat-free mass and fat mass content was evaluated using multiple linear regression analysis; (3) Results: Human milk was fed to 68% of the infants. According to multiple regression analysis, being fed any human milk at discharge and at  term-corrected and being fed exclusively human milk at term-corrected age were positively associated with fat-free mass content(β = -47.9, 95% confidence interval (CI) = -95.7; -0.18; p = 0.049; β = -89.6, 95% CI = -131.5; -47.7; p < 0.0001; β = -104.1, 95% CI = -151.4; -56.7, p < 0.0001); (4) Conclusion: Human milk feeding appears to be associated with fat-free mass deposition in late preterm infants. Healthcare professionals should direct efforts toward promoting and supporting breastfeeding in these vulnerable infants.

  18. Involvement of F-BOX proteins in progression and development of human malignancies.

    PubMed

    Uddin, Shahab; Bhat, Ajaz A; Krishnankutty, Roopesh; Mir, Fayaz; Kulinski, Michal; Mohammad, Ramzi M

    2016-02-01

    The Ubiquitin Proteasome System (UPS) is a core regulator with various protein components (ubiquitin-activating E1 enzymes, ubiquitin-conjugating E2 enzymes, ubiquitin-protein E3 ligases, and the 26S proteasome) which work together in a coordinated fashion to ensure the appropriate and efficient proteolysis of target substrates. E3 ubiquitin ligases are essential components of the UPS machinery, working with E1 and E2 enzymes to bind substrates and assist the transport of ubiquitin molecules onto the target protein. As the UPS controls the degradation of several oncogenes and tumor suppressors, dysregulation of this pathway leads to several human malignancies. A major category of E3 Ub ligases, the SCF (Skp-Cullin-F-box) complex, is composed of four principal components: Skp1, Cul1/Cdc53, Roc1/Rbx1/Hrt1, and an F-box protein (FBP). FBPs are the substrate recognition components of SCF complexes and function as adaptors that bring substrates into physical proximity with the rest of the SCF. Besides acting as a component of SCF complexes, FBPs are involved in DNA replication, transcription, cell differentiation and cell death. This review will highlight the recent literature on three well characterized FBPs SKP2, Fbw7, and beta-TRCP. In particular, we will focus on the involvement of these deregulated FBPs in the progression and development of various human cancers. We will also highlight some novel substrates recently identified for these FBPs.

  19. Production of Human Pluripotent Stem Cell Therapeutics Under Defined Xeno-free Conditions: Progress and Challenges

    PubMed Central

    Fan, Yongjia; Wu, Jincheng; Ashok, Preeti; Hsiung, Michael; Tzanakakis, Emmanuel S.

    2014-01-01

    Recent advances on human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) have brought us closer to the realization of their clinical potential. Nonetheless, tissue engineering and regenerative medicine applications will require the generation of hPSC products well beyond the laboratory scale. This also mandates the production of hPSC therapeutics in fully-defined, xeno-free systems and in a reproducible manner. Toward this goal, we summarize current developments in defined media free of animal-derived components for hPSC culture. Bioinspired and synthetic extracellular matrices for the attachment growth and differentiation of hPSCs are also reviewed. Given that most progress in xeno-free medium and substrate development has been demonstrated in two-dimensional rather than three dimensional culture systems, translation from the former to the latter poses unique difficulties. These challenges are discussed in the context of cultivation platforms of hPSCs as aggregates, on microcarriers or after encapsulation in biocompatible scaffolds. PMID:25077810

  20. The Prevalence and Distribution of Aging-Friendly Human Resource Practices.

    PubMed

    Segel-Karpas, Dikla; Bamberger, Peter A; Bacharach, Samuel B

    2015-07-01

    The aging of the workforce in the developed world has prompted organizations to implement human resource (HR) policies and practices encouraging older workers to defer retirement. However, little is known about the prevalence of such practices, and the organizational factors associated with their adoption. In this study, we used data collected from 2008 to 2009 from a national probability sample of retirement eligible workers in the United States (N = 407) to assess the prevalence of aging-friendly human resource practices (AFHRP), and their organizational predictors. Results indicate that employee wellness programs, unpaid leave, and reassignment based on physical needs are among the most prevalent AFHRP. However, in the vast majority of enterprises, AFHRP are limited. Results also indicate that projected organizational growth and a focus on internal labor market practices are positively associated with the adoption of AFHRP. Organizational size and the degree of unionization, while positively associated with aging-friendly benefits, were inversely associated with flexibility practices.

  1. Nested PCR-denaturing gradient gel electrophoresis analysis of human skin microbial diversity with age.

    PubMed

    Li, Wei; Han, Lei; Yu, Pengbo; Ma, Chaofeng; Wu, Xiaokang; Xu, Jiru

    2014-01-01

    To determine whether the composition and structure of skin microbiota differ with age, cutaneous bacteria were isolated from the axillary fossa of 37 healthy human adults in two age groups (old people and young adults). Bacterial genomic DNA was extracted and characterized by nested PCR-denaturing gradient gel electrophoresis (PCR-DGGE) with primers specifically targeting V3 region of the 16S rRNA gene. The excised gel bands were sequenced to identify bacterial categories. The total bacteria, Staphylococcus spp., Staphylococcus epidermidis and Corynebacterium spp. were further enumerated by quantitative PCR. There were no significant differences in the species diversity profiles between age groups. The similarity index was lower across age groups than that it was intra-group. This indicates that the composition of skin flora is more similar to others of the same age than across age groups. While Staphylococcus spp. and Corynebacterium spp. were the dominant bacteria in both groups, sequencing and quantitative PCR revealed that skin bacterial composition differed by age. The copy number of total bacteria and Corynebacterium spp. were significantly lower in younger subjects, whereas there were no statistical differences in the quantity of Staphylococcus spp. and Staphylococcus epidermidis. These results suggest that the skin flora undergo both quantitative and qualitative changes related to aging.

  2. Longitudinal psychomotor speed performance in human immunodeficiency virus-seropositive individuals: impact of age and serostatus.

    PubMed

    Sacktor, Ned; Skolasky, Richard L; Cox, Christopher; Selnes, Ola; Becker, James T; Cohen, Bruce; Martin, Eileen; Miller, Eric N

    2010-10-01

    Older human immunodeficiency virus-seropositive (HIV+) individuals (greater than age 50 years) are twice as likely to develop HIV dementia compared to younger HIV+ individuals. The objective of this study was to examine the impact of both age and serostatus on longitudinal changes in psychomotor speed/executive functioning performance among HIV+ and HIV− individuals. Four hundred and seventy-seven HIV+ and 799 HIV− individuals from the Multicenter AIDS Cohort Study (MACS) were subdivided into three age groups: (1) <40 years, (2) 40-50 years, and (3) >50 years. Psychomotor speed/executive functioning test performance was measured by the Symbol Digit Modalities Test (SDMT) and the Trail Making (TM) Test Parts A and B. Changes in performance were compared among the three age groups for both HIV+ and HIV− individuals. Among HIV+ individuals, on the TM Test Part B the younger group demonstrated improvement in performance over time (P = .007). The older and middle age groups demonstrated decline in performance over time (P = .041 and .030). The older group had a significantly different trajectory relative to the younger group (P = .046). Among the HIV− individuals, there was no effect of age on longitudinal performance. In conclusion, older HIV+ individuals show greater decline over time than younger HIV+ individuals on the TM Test Part B. Our results suggest that both HIV serostatus and age together may impact longitudinal performance on this test. Mild neurocognitive changes over time among older HIV+ individuals are likely to reflect age associated pathophysiological mechanisms including cerebrovascular risk factors.

  3. HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging.

    PubMed

    Jazwinski, S Michal; Kim, Sangkyu; Dai, Jianliang; Li, Li; Bi, Xiuhua; Jiang, James C; Arnold, Jonathan; Batzer, Mark A; Walker, Jerilyn A; Welsh, David A; Lefante, Christina M; Volaufova, Julia; Myers, Leann; Su, L Joseph; Hausman, Dorothy B; Miceli, Michael V; Ravussin, Eric; Poon, Leonard W; Cherry, Katie E; Welsch, Michael A

    2010-10-01

    The search for longevity-determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity. An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population. A profile of healthy aging was developed using a deficit accumulation index, which showed that this combination of gene variants is associated with healthy aging. The variation in LASS1 is functional, causing enhanced expression of the gene, and it contributes to healthy aging and greater survival in the tenth decade of life. Thus, rare gene variants need not be invoked to explain complex traits such as aging; instead rare congruence of common gene variants readily fulfills this role. The interaction between the three genes described here suggests new models for cellular and molecular mechanisms underlying exceptional survival and healthy aging that involve lipotoxicity.

  4. Confocal Raman study of aging process in diabetes mellitus human voluntaries

    NASA Astrophysics Data System (ADS)

    Pereira, Liliane; Téllez Soto, Claudio Alberto; dos Santos, Laurita; Ali, Syed Mohammed; Fávero, Priscila Pereira; Martin, Airton A.

    2015-06-01

    Accumulation of AGEs [Advanced Glycation End - products] occurs slowly during the human aging process. However, its formation is accelerated in the presence of diabetes mellitus. In this paper, we perform a noninvasive analysis of glycation effect on human skin by in vivo confocal Raman spectroscopy. This technique uses a laser of 785 nm as excitation source and, by the inelastic scattering of light, it is possible to obtain information about the biochemical composition of the skin. Our aim in this work was to characterize the aging process resulting from the glycation process in a group of 10 Health Elderly Women (HEW) and 10 Diabetic Elderly Women (DEW). The Raman data were collected from the dermis at a depth of 70-130 microns. Through the theory of functional density (DFT) the bands positions of hydroxyproline, proline and AGEs (pentosidine and glucosepane) were calculated by using Gaussian 0.9 software. A molecular interpretation of changes in type I collagen was performed by the changes in the vibrational modes of the proline (P) and hydroxyproline (HP). The data analysis shows that the aging effects caused by glycation of proteins degrades type I collagen differently and leads to accelerated aging process.

  5. Increased human AP endonuclease 1 level confers protection against the paternal age effect in mice

    PubMed Central

    Sanchez, Jamila R.; Reddick, Traci L.; Perez, Marissa; Centonze, Victoria E.; Mitra, Sankar; Izumi, Tadahide; McMahan, C. Alex; Walter, Christi A.

    2015-01-01

    Increased paternal age is associated with a greater risk of producing children with genetic disorders originating from de novo germline mutations. Mice mimic the human condition by displaying an age-associated increase in spontaneous mutant frequency in spermatogenic cells. The observed increase in mutant frequency appears to be associated with a decrease in the DNA repair protein, AP endonuclease1 (APEX1) and Apex1 heterozygous mice display an accelerated paternal age effect as young adults. In this study, we directly tested if APEX1 over-expression in cell lines and transgenic mice could prevent increases in mutagenesis. Cell lines with ectopic expression of APEX1 had increased APEX1 activity and lower spontaneous and induced mutations in the lacI reporter gene relative to the control. Spermatogenic cells obtained from mice transgenic for human APEX1 displayed increased APEX1 activity, were protected from the age-dependent increase in spontaneous germline mutagenesis, and exhibited increased apoptosis in the spermatogonial cell population. These results directly indicate that increases in APEX1 level confer protection against the murine paternal age effect, thus highlighting the role of APEX1 in preserving reproductive health with increasing age and in protection against genotoxin-induced mutagenesis in somatic cells. PMID:26201249

  6. Essential Microenvironment for Thymopoiesis is Preserved in Human Adult and Aged Thymus

    PubMed Central

    Shiraishi, J.; Utsuyama, M.; Seki, S.; Akamatsu, H.; Sunamori, M.; Kasai, M.; Hirokawa, K.

    2003-01-01

    Normal human thymuses at various ages were immunohistologically examined in order to determine whether adult or aged thymus maintained the microenvironment for the T cell development and thymopoiesis was really ongoing. To analyze the thymic microenvironment, two monoclonal antibodies (MoAb) were employed. One is MoAb to IL-1 receptor (IL-1R) recognizing medullary and subcapsular cortical epithelial cells of normal infant human thymus. The other is UH-1 MoAb recognizing thymic epithelial cells within the cortex, which are negative with IL-1R-MoAb. Thymus of subjects over 20 years of age was split into many fragments and dispersed in the fatty tissue. However, the microenvironment of each fragment was composed of both IL-1R positive and UH-1 positive epithelial cells, and the UH-1 positive portion was populated with lymphocytes showing a follicle-like appearance. Lymphocytes in these follicle-like portions were mostly CD4+CD8+ double positive cells and contained many proliferating cells as well as apoptotic cells. Thus these follicle-like portions in adult and aged thymus were considered to be functioning as cortex as in infant thymus. Proliferative activity of thymocytes in the thymic cortex and the follicle-like portions definitely declined with advance of age, while incidence of apoptotic thymocytes increased with aging. PMID:14575158

  7. Influence of sex, smoking and age on human hprt mutation frequencies and spectra.

    PubMed Central

    Curry, J; Karnaoukhova, L; Guenette, G C; Glickman, B W

    1999-01-01

    Examination of the literature for hprt mutant frequencies from peripheral T cells yielded data from 1194 human subjects. Relationships between mutant frequency, age, sex, and smoking were examined, and the kinetics were described. Mutant frequency increases rapidly with age until about age 15. Afterward, the rate of increase falls such that after age 53, the hprt mutant frequency is largely stabilized. Sex had no effect on mutant frequency. Cigarette smoking increased mean mutant frequency compared to nonsmokers, but did not alter age vs. mutant frequency relationships. An hprt in vivo mutant database containing 795 human hprt mutants from 342 individuals was prepared. No difference in mutational spectra was observed comparing smokers to nonsmokers, confirming previous reports. Sex affected the frequency of deletions (>1 bp) that are recovered more than twice as frequently in females (P = 0. 008) compared to males. There is no indication of a significant shift in mutational spectra with age for individuals older than 19 yr, with the exception of A:T --> C:G transversions. These events are recovered more frequently in older individuals. PMID:10388825

  8. Analysis of age and gender associated N-glycoproteome in human whole saliva

    PubMed Central

    2014-01-01

    Background Glycoproteins comprise a large portion of the salivary proteome and have great potential for biomarker discovery and disease diagnosis. However, the rate of production and the concentration of whole saliva change with age, gender and physiological states of the human body. Therefore, a thorough understanding of the salivary glycoproteome of healthy individuals of different ages and genders is a prerequisite for saliva to have clinical utility. Methods Formerly N-linked glycopeptides were isolated from the pooled whole saliva of six age and gender groups by hydrazide chemistry and hydrophilic affinity methods followed by mass spectrometry identification. Selected physiochemical characteristics of salivary glycoproteins were analyzed, and the salivary glycoproteomes of different age and gender groups were compared based on their glycoprotein components and gene ontology. Results and discussion Among 85 N-glycoproteins identified in healthy human saliva, the majority were acidic proteins with low molecular weight. The numbers of salivary N-glycoproteins increased with age. Fifteen salivary glycoproteins were identified as potential age- or gender-associated glycoproteins, and many of them have functions related to innate immunity against microorganisms and oral cavity protection. Moreover, many salivary glycoproteins have been previously reported as disease related glycoproteins. This study reveals the important role of salivary glycoproteins in the maintenance of oral health and homeostasis and the great potential of saliva for biomarker discovery and disease diagnosis. PMID:24994967

  9. Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes

    SciTech Connect

    Vaziri, H.; Uchida, I.; Lan Wei; Harley, C.B. ); Schaechter, F.; Cohen, D. ); Xiaoming Zhu; Effros, R. )

    1993-04-01

    The telomere hypothesis of cellular aging proposes that loss of telomeric DNA (TTAGGG) from human chromosomes may ultimately cause cell-cycle exit during replicative senescence. Since lymphocytes have a limited replicative capacity and since blood cells were previously shown to lose telomeric DNA during aging in vivo, the authors wished to determine (a) whether accelerated telomere loss is associated with the premature immunosenescence of lymphocytes in individuals with Down syndrome (DS) and (b) whether telomeric DNA is also lost during aging of lymphocytes in vitro. To investigate the effects of aging and trisomy 21 on telomere loss in vivo, genomic DNA was isolated from peripheral blood lymphocytes of 140 individuals (age 0--107 years), including 21 DS patients (age 0--45 years). Digestion with restriction enzymes HinfI and RsaI generated terminal restriction fragments (TRFs), which were detected by Southern analysis using a telomere-specific probe ([sup 32]P-(C[sub 3]TA[sub 2])[sub 3]). The rate of telomere loss was calculated from the decrease in mean TRF length, as a function of donor age. DS patients showed a significantly higher rate of telomere loss with donor age (133 [+-] 15 bp/year) compared with age-matched controls (41 [+-] 7.7 bp/year) (P < .0005), suggesting that accelerated telomere loss is a biomarker of premature immunosenescence of DS patients and that it may play a role in this process. Telomere loss during aging in vitro was calculated for lymphocytes from four normal individuals, grown in culture for 10--30 population doublings. The rate of telomere loss was [approximately]120 bp/cell doubling, comparable to that seen in other somatic cells. Moreover, telomere lengths of lymphocytes from centenarians and from older DS patients were similar to those of senescent lymphocytes in culture, which suggests that replicative senescence could partially account for aging of the immune system in DS patients and in elderly individuals. 31 refs., 3 figs.

  10. Femoral neck-shaft angle in humans: variation relating to climate, clothing, lifestyle, sex, age and side.

    PubMed

    Gilligan, Ian; Chandraphak, Supichya; Mahakkanukrauh, Pasuk

    2013-08-01

    The femoral neck-shaft angle (NSA) varies among modern humans but measurement problems and sampling limitations have precluded the identification of factors contributing to its variation at the population level. Potential sources of variation include sex, age, side (left or right), regional differences in body shape due to climatic adaptation, and the effects of habitual activity patterns (e.g. mobile and sedentary lifestyles and foraging, agricultural, and urban economies). In this study we addressed these issues, using consistent methods to assemble a global NSA database comprising over 8000 femora representing 100 human groups. Results from the analyses show an average NSA for modern humans of 127° (markedly lower than the accepted value of 135°); there is no sex difference, no age-related change in adults, but possibly a small lateral difference which could be due to right leg dominance. Climatic trends consistent with principles based on Bergmann's rule are evident at the global and continental levels, with the NSA varying in relation to other body shape indices: median NSA, for instance, is higher in warmer regions, notably in the Pacific (130°), whereas lower values (associated with a more stocky body build) are found in regions where ancestral populations were exposed to colder conditions, in Europe (126°) and the Americas (125°). There is a modest trend towards increasing NSA with the economic transitions from forager to agricultural and urban lifestyles and, to a lesser extent, from a mobile to a sedentary existence. However, the main trend associated with these transitions is a progressive narrowing in the range of variation in the NSA, which may be attributable to thermal insulation provided by improved cultural buffering from climate, particularly clothing.

  11. Femoral neck-shaft angle in humans: variation relating to climate, clothing, lifestyle, sex, age and side

    PubMed Central

    Gilligan, Ian; Chandraphak, Supichya; Mahakkanukrauh, Pasuk

    2013-01-01

    The femoral neck-shaft angle (NSA) varies among modern humans but measurement problems and sampling limitations have precluded the identification of factors contributing to its variation at the population level. Potential sources of variation include sex, age, side (left or right), regional differences in body shape due to climatic adaptation, and the effects of habitual activity patterns (e.g. mobile and sedentary lifestyles and foraging, agricultural, and urban economies). In this study we addressed these issues, using consistent methods to assemble a global NSA database comprising over 8000 femora representing 100 human groups. Results from the analyses show an average NSA for modern humans of 127° (markedly lower than the accepted value of 135°); there is no sex difference, no age-related change in adults, but possibly a small lateral difference which could be due to right leg dominance. Climatic trends consistent with principles based on Bergmann's rule are evident at the global and continental levels, with the NSA varying in relation to other body shape indices: median NSA, for instance, is higher in warmer regions, notably in the Pacific (130°), whereas lower values (associated with a more stocky body build) are found in regions where ancestral populations were exposed to colder conditions, in Europe (126°) and the Americas (125°). There is a modest trend towards increasing NSA with the economic transitions from forager to agricultural and urban lifestyles and, to a lesser extent, from a mobile to a sedentary existence. However, the main trend associated with these transitions is a progressive narrowing in the range of variation in the NSA, which may be attributable to thermal insulation provided by improved cultural buffering from climate, particularly clothing. PMID:23781912

  12. When New Media Meet the Strong Web of Connected Learning Environments: A New Vision of Progressive Education in the Digital Age

    ERIC Educational Resources Information Center

    Nam, Chaebong

    2013-01-01

    This paper shows how the legacy of Jane Addams' socialized education can live on in today's progressive education, especially in the digital age. Discussion is drawn from a case study of an anti-underage drinking campaign conducted by urban youth of color in an afterschool program. The media ecology environment in the campaign--the integrated…

  13. Individual variability in human blood metabolites identifies age-related differences

    PubMed Central

    Murakami, Itsuo; Takada, Junko; Kondoh, Hiroshi; Yanagida, Mitsuhiro

    2016-01-01

    Metabolites present in human blood document individual physiological states influenced by genetic, epigenetic, and lifestyle factors. Using high-resolution liquid chromatography-mass spectrometry (LC-MS), we performed nontargeted, quantitative metabolomics analysis in blood of 15 young (29 ± 4 y of age) and 15 elderly (81 ± 7 y of age) individuals. Coefficients of variation (CV = SD/mean) were obtained for 126 blood metabolites of all 30 donors. Fifty-five RBC-enriched metabolites, for which metabolomics studies have been scarce, are highlighted here. We found 14 blood compounds that show remarkable age-related increases or decreases; they include 1,5-anhydroglucitol, dimethyl-guanosine, acetyl-carnosine, carnosine, ophthalmic acid, UDP-acetyl-glucosamine, N-acetyl-arginine, N6-acetyl-lysine, pantothenate, citrulline, leucine, isoleucine, NAD+, and NADP+. Six of them are RBC-enriched, suggesting that RBC metabolomics is highly valuable for human aging research. Age differences are partly explained by a decrease in antioxidant production or increasing inefficiency of urea metabolism among the elderly. Pearson’s coefficients demonstrated that some age-related compounds are correlated, suggesting that aging affects them concomitantly. Although our CV values are mostly consistent with those CVs previously published, we here report previously unidentified CVs of 51 blood compounds. Compounds having moderate to h