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Sample records for aging human lens

  1. Light scattering study of the normal human eye lens: Elastic properties and age dependence

    PubMed Central

    Bailey, Sheldon T.; Twa, Michael D.; Gump, Jared C.; Venkiteshwar, Manoj; Bullimore, Mark A.

    2015-01-01

    The human ocular lens is a tissue capable of changing its shape to dynamically adjust the optical power of the eye, a function known as accommodation, which gradually declines with age. This capability is the response of the lens tissue to external forces which, in turn, is modulated by the biomechanical characteristics of lens tissues. In order to investigate the contributions of lens sclerosis to loss of accommodation, we report on in vitro confocal Brillouin light scattering studies of human ocular lenses spanning over a 30-70 year age range. Using this non-destructive measurement method, we determined that the longitudinal bulk modulus (average ± SD) of the lens nucleus (2.79±0.14 GPa) was consistently greater than the bulk modulus of the lens cortex (2.36±0.09 GPa). Moreover, our results showed that these differences were not age dependent over the 40 year age range that we evaluated using healthy lens tissues. Our results are consistent with the hypothesis that an age-dependent change in the bulk modulus of lens tissues does not fully account for the natural decline of accommodation. PMID:20529725

  2. Biometric, optical and physical changes in the isolated human crystalline lens with age in relation to presbyopia.

    PubMed

    Glasser, A; Campbell, M C

    1999-06-01

    The biometric, optical and physical properties of 19 pairs of isolated human eye-bank lenses ranging in age from 5 to 96 years were compared. Lens focal length and spherical aberration were measured using a scanning laser apparatus, lens thickness and the lens surface curvatures were measured by digitizing the lens profiles and equivalent refractive indices were calculated for each lens using this data. The second lens from each donor was used to measure resistance to physical deformation by providing a compressive force to the lens. The lens capsule was then removed from each lens and each measurement was repeated to ascertain what role the capsule plays in determining these optical and physical characteristics. Age dependent changes in lens focal length, lens surface curvatures and lens resistance to physical deformation are described. Isolated lens focal length was found to be significantly linearly correlated with both the anterior and posterior surface curvatures. No age dependent change in equivalent refractive index of the isolated lens was found. Although decapsulating human lenses causes similar changes in focal length to that which we have shown to occur when human lenses are mechanically stretched into an unaccommodated state, the effects are due to nonsystematic changes in lens curvatures. These studies reinforce the conclusion that lens hardening must be considered as an important factor in the development of presbyopia, that age changes in the human lens are not limited to the loss of accommodation that characterizes presbyopia but that the lens optical and physical properties change substantially with age in a complex manner.

  3. 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.

  4. 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

  5. Protocatechualdehyde prevents methylglyoxal-induced mitochondrial dysfunction and AGEs-RAGE axis activation in human lens epithelial cells.

    PubMed

    Wang, Yue-Hua; Han, Yu-Pei; Yu, Hai-Tao; Pu, Xiao-Ping; Du, Guan-Hua

    2014-09-05

    Methylglyoxal (MGO), a glucose derived dicarbonyl intermediate, is a major precursor of advanced glycation end products (AGEs) which have been linked to the development of diabetic cataract. Protocatechualdehyde (PCA), a phenolic acid compound, is found in the roots of Salvia miltiorrhiza. This study was to investigate the effect of PCA against MGO-induced cytotoxicity in human lens epithelial cells (SRA01/04 cells) and the possible involved molecular mechanism. The results showed that PCA alleviated MGO-induced mitochondrial dysfunction and apoptosis in SRA01/04 cells. Furthermore, PCA was capable of inhibiting MGO-mediated AGEs formation and blocking receptor of AGEs expression in SRA01/04 cells. It is concluded that PCA could be useful in attenuation of MGO-induced cell damage and the possible mechanism is involved in modulating AGEs-receptor of AGEs axis in human lens epithelial cells, which suggests that PCA has a potential protective effect on diabetic cataract.

  6. 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

  7. Lens Aging: Effects of Crystallins

    PubMed Central

    Sharma, K. Krishna; Santhoshkumar, Puttur

    2009-01-01

    The primary function of the eye lens is to focus light on the retina. The major proteins in the lens—a, b, and g-crystallins—are constantly subjected to age-related changes such as oxidation, deamidation, truncation, glycation, and methylation. Such age-related modifications are cumulative and affect crystallin structure and function. With time, the modified crystallins aggregate, causing the lens to increasingly scatter light on the retina instead of focusing light on it and causing the lens to lose its transparency gradually and become opaque. Age-related lens opacity, or cataract, is the major cause of blindness worldwide. We review deamidation, and glycation that occur in the lenses during aging keeping in mind the structural and functional changes that these modifications bring about in the proteins. In addition, we review proteolysis and discuss recent observations on how crystallin fragments generated in vivo, through their anti-chaperone activity may cause crystallin aggregation in aging lenses. We also review hyperbaric oxygen treatment induced guinea pig and ‘humanized’ ascorbate transporting mouse models as suitable options for studies on age-related changes in lens proteins. PMID:19463898

  8. Identification and Functional Assessment of Age-Dependent Truncations to Cx46 and Cx50 in the Human Lens

    PubMed Central

    Slavi, Nefeli; Wang, Zhen; Harvey, Lucas; Schey, Kevin L.; Srinivas, Miduturu

    2016-01-01

    Purpose Many proteins in the lens undergo extensive posttranslational modifications (PTMs) with age, leading to alterations in their function. The extent to which lens gap junction proteins, Cx46 and Cx50, accumulate PTMs with aging is not known. In this study, we identified truncations in Cx46 and Cx50 in the human lens using mass spectrometry. We also examined the effect of truncations on channel function using electrophysiological measurements. Methods Human lenses were dissected into cortex, outer nucleus, and nucleus regions, and fiber cell membranes were subjected to trypsin digestion. Tryptic peptides were analyzed by liquid chromatography (LC)–electrospray tandem mass spectrometry (ESI/MS/MS). Effects of truncations on channel conductance, permeability, and gating were assessed in transfected cells. Results Cleavage sites were identified in the C-terminus, the cytoplasmic loop, and the N-terminus of Cx46 and Cx50. Levels of C-terminal truncations, which were found at residues 238 to 251 in Cx46 and at residues 238 to 253 and 274 to 284 in Cx50, were similar in different lens regions. In contrast, levels of truncations in cytoplasmic loop and N-terminal domains of Cx46 and Cx50 increased dramatically from outer cortex to nucleus. Most of the C-terminally truncated proteins were functional, whereas truncations in the cytoplasmic loop did not result in the formation of functional channels. Conclusions Accumulation of cytoplasmic loop and N-terminal truncations in the core might lead to decreases in coupling with age. This reduction is expected to lead to an increase in intracellular calcium and a decrease in levels of glutathione in the nucleus. These changes may ultimately lead to age-related nuclear cataracts. PMID:27787559

  9. Interaction of intraocular lenses with fibronectin and human lens epithelial cells: Effect of chemical composition and aging.

    PubMed

    Tortolano, Lionel; Serrano, Carole; Jubeli, Emile; Saunier, Johanna; Yagoubi, Najet

    2015-12-01

    The aim of this study is to investigate in vitro interactions between hydrophobic acrylate intraocular lenses (IOLs) and their biological environment. The influence of lens chemical composition and aging on fibronectin (FN) adsorption and on IOLs cytotoxicity on human lens epithelial cells was examined. Cytotoxicity of acrylate monomers used in IOLs manufacture was also investigated. Four different IOLs were included in the study: Acrysof(®), Tecnis(®), EnVista(®), and iSert(®). Implants were artificially aged in a xenon arc chamber to simulate 2 years of light exposure. Fibronectin adsorption on IOL surface was quantified using ELISA and correlated to surface roughness determined with AFM. Direct contact cytotoxicity was determined with the MTT assay and cell morphology was observed with light microscopy. Results showed that fibronectin adsorption did not differ significantly among IOLs, whatever their chemical composition. Moreover, aging conditions did not impact fibronectin adsorption. All IOLs were biocompatible even after applying 2-year aging conditions, with cell viability higher than 70%. Five acrylate monomers appeared to be toxic in the range of concentrations tested, but no monomer release from the IOLs could be detected during accelerated 2-year incubation with saline solution. This study did not reveal an influence of chemical composition and aging on protein adsorption and on biocompatibility.

  10. Identification of the in vivo truncation sites at the C-terminal region of alpha-A crystallin from aged bovine and human lens

    NASA Technical Reports Server (NTRS)

    Takemoto, L. J.; Spooner, B. S. (Principal Investigator)

    1995-01-01

    Total alpha-A crystallin was purified from young versus old lens, followed by digestion with cyanogen bromide. Laser desorption mass spectrometry of the C-terminal fragment demonstrated age-dependent loss of one and five amino acids from the C-terminus of alpha-A crystallin from both bovine and human lens. These results demonstrate specific peptide bonds of alpha-A crystallin are cleaved during the aging process of the normal lens. The C-terminal region is cleaved in two places between the two hydroxyl-containing amino acids present in the sequence -P-S(T)-S-.

  11. In Vivo Brillouin Analysis of the Aging Crystalline Lens

    PubMed Central

    Besner, Sebastien; Scarcelli, Giuliano; Pineda, Roberto; Yun, Seok-Hyun

    2016-01-01

    Purpose To analyze the age dependence of the longitudinal modulus of the crystalline lens in vivo using Brillouin scattering data in healthy subjects. Methods Brillouin scans were performed along the crystalline lens in 56 eyes from 30 healthy subjects aged from 19 to 63 years. Longitudinal elastic modulus was acquired along the sagittal axis of the lens with a transverse and axial resolution of 4 and 60 μm, respectively. The relative lens stiffness was computed, and correlations with age were analyzed. Results Brillouin axial profiles revealed nonuniform longitudinal modulus within the lens, increasing from a softer periphery toward a stiffer central plateau at all ages. The longitudinal modulus at the central plateau showed no age dependence in a range of 19 to 45 years and a slight decrease with age from 45 to 63 years. A significant intersubject variability was observed in an age-matched analysis. Importantly, the extent of the central stiff plateau region increased steadily over age from 19 to 63 years. The slope of change in Brillouin modulus in the peripheral regions were nearly age-invariant. Conclusions The adult human lens showed no measurable age-related increase in the peak longitudinal modulus. The expansion of the stiff central region of the lens is likely to be the major contributing factor to age-related lens stiffening. Brillouin microscopy may be useful in characterizing the crystalline lens for the optimization of surgical or pharmacological treatments aimed at restoring accommodative power. PMID:27699407

  12. Growth of the human eye lens

    PubMed Central

    2007-01-01

    Purpose To analyze human lens growth from the accumulation of wet weight as a function of age. Methods Wet weights were assembled for over 1,100 human lenses, ranging in age from 6 months prenatal to 99 years postnatal, and were examined using various growth models. Initially, prenatal and postnatal data were examined separately, to determine the growth modes and then all data were fitted to a single equation. Results Variations in weights due to tissue handling procedures and the unavailability of statistical data for averaged sets precluded the use of >500 values in the present analysis. Regression of age on log lens weight for the remaining 614 lenses indicated that, unlike other species, human lens growth appears to take place in two distinct phases. It was found that asymptotic growth during prenatal life and early childhood generates about 149 mg of tissue in a process, which can be modelled with a Gompertz function. Soon after birth, growth becomes linear, dropping to 1.38 mg/year, and this rate is maintained throughout the rest of life. The relationship of lens wet weight with age over the whole of the lifespan could best be described with the expression, W=1.38Ab + 149exp^[exp^(1.6-3Ac)], where W is lens weight in mg, Ab is postnatal age in years and Ac is the time since conception in years. Comparison of 138 male and 64 female lenses indicated that there was no statistically significant difference between male and female lens weights in the linear (adult) growth mode. Conclusions Human lens growth differs from growth in other species in that it occurs in two distinct modes. The first follows a sigmoidal relationship and provides an initial burst of rapid growth during prenatal development with an apparent termination at or shortly after birth. The second growth mode is linear, adding 1.38 mg/year to lens wet weight, throughout life. Because of the variability in available lens wet weight data, further studies, preferably using lens dry weights or protein

  13. An experimental and clinical evaluation of lens transparency and aging.

    PubMed

    Lerman, S

    1983-05-01

    The normal human lens is a precisely formed structure containing about 65% water and 35% organic matter, the latter being mainly (greater than 90%) structural proteins. The lens becomes encapsulated at the 13 mm embryonic stage and is consequently divorced from a direct blood supply for life. It provides the investigator with an organ that exists in an environment analogous to a single-cell type of tissue culture system and can be reproduced in vitro. Since the cornea and lens are transparent one can directly monitor morphologic and biochemical aging changes in vivo. Recent developments now permit us to monitor certain molecular changes as well. Thus this organ can serve as a unique model for studying in vivo aging parameters. In vivo UV slit lamp densitography to monitor lens fluorescence provides us with a useful diagnostic and prognostic screening method to identify lens photodamage due to excess UV exposure (occupational or accidental), photosensitizers (e.g. psoralens) as well as the normal age related increase in lenticular fluorescence. Cortical opacities are also a common finding in older individuals. In vitro NMR (human and animal lenses) and in vivo (animal experiments) currently in progress are rapidly elucidating the physicochemical basis for the development of light scattering areas in the aging lens cortex. This review demonstrates the feasibility of utilizing biophysical methods, in particular, optical spectroscopy and NMR analyses to delineate and monitor specific age related parameters in the ocular lens, in vivo as well as in vitro.

  14. Age-dependence of the optomechanical responses of ex vivo human lenses from India and the USA, and the force required to produce these in a lens stretcher: the similarity to in vivo disaccommodation

    PubMed Central

    Augusteyn, Robert C; Mohamed, Ashik; Nankivil, Derek; Veerendranath, Pesala; Arrieta, Esdras; Taneja, Mukesh; Manns, Fabrice; Ho, Arthur; Parel, Jean-Marie

    2011-01-01

    The purpose of this study was to study the age-dependence of the optomechanical properties of human lenses during simulated disaccommodation in a mechanical lens stretcher, designed to determine accommodative forces as a function of stretch distance, to compare the results with in vivo disaccommodation and to examine whether differences exist between eyes harvested in the USA and India. Post-mortem human eyes obtained in the USA (n=46, age = 6 to 83 years) and India (n=91, age = 1 day to 85 years) were mounted in an optomechanical lens stretching system and dissected to expose the lens complete with its accommodating framework, including zonules, ciliary body, anterior vitreous and a segmented rim of sclera. Disaccommodation was simulated through radial stretching of the sectioned globe by 2 mm in increments of 0.25 mm. The load, inner ciliary ring diameter, lens equatorial diameter, central thickness and power were measured at each step. Changes in these parameters were examined as a function of age, as were the dimension/load and power/load responses. Unstretched lens diameter and thickness increased over the whole age range examined and were indistinguishable from those of in vivo lenses as well as those of in vitro lenses freed from zonular attachments. Stretching increased the diameter and decreased the thickness in all lenses examined but the amount of change decreased with age. Unstretched lens power decreased with age and the accommodative amplitude decreased to zero by age 45-50. The load required to produce maximum stretch was independent of age (median 80 mN) whereas the change in lens diameter and power per unit load decreased significantly with age. The age related changes in the properties of human lenses, as observed in the lens stretching device, are similar to those observed in vivo and are consistent with the classical Helmholtz theory of accommodation. The response of lens diameter and power to disaccommodative (stretching) forces decreases with

  15. Intrinsically photosensitive retinal ganglion cell function in relation to age: A pupillometric study in humans with special reference to the age-related optic properties of the lens

    PubMed Central

    2012-01-01

    Background The activity of melanopsin containing intrinsically photosensitive ganglion retinal cells (ipRGC) can be assessed by a means of pupil responses to bright blue (appr.480 nm) light. Due to age related factors in the eye, particularly, structural changes of the lens, less light reaches retina. The aim of this study was to examine how age and in vivo measured lens transmission of blue light might affect pupil light responses, in particular, mediated by the ipRGC. Methods Consensual pupil responses were explored in 44 healthy subjects aged between 26 and 68 years. A pupil response was recorded to a continuous 20 s light stimulus of 660 nm (red) or 470 nm (blue) both at 300 cd/m2 intensity (14.9 and 14.8 log photons/cm2/s, respectively). Additional recordings were performed using four 470 nm stimulus intensities of 3, 30, 100 and 300 cd/m2. The baseline pupil size was measured in darkness and results were adjusted for the baseline pupil and gender. The main outcome parameters were maximal and sustained pupil contraction amplitudes and the postillumination response assessed as area under the curve (AUC) over two time-windows: early (0–10 s after light termination) and late (10–30 s after light termination). Lens transmission was measured with an ocular fluorometer. Results The sustained pupil contraction and the early poststimulus AUC correlated positively with age (p = 0.02, p = 0.0014, respectively) for the blue light stimulus condition only. The maximal pupil contraction amplitude did not correlate to age either for bright blue or red light stimulus conditions. Lens transmission decreased linearly with age (p < 0.0001). The pupil response was stable or increased with decreasing transmission, though only significantly for the early poststimulus AUC to 300 cd/m2 light (p = 0.02). Conclusions Age did not reduce, but rather enhance pupil responses mediated by ipRGC. The age related decrease of blue light transmission led

  16. Methylglyoxal induces endoplasmic reticulum stress and DNA demethylation in the Keap1 promoter of human lens epithelial cells and age-related cataracts.

    PubMed

    Palsamy, Periyasamy; Bidasee, Keshore R; Ayaki, Masahiko; Augusteyn, Robert C; Chan, Jefferson Y; Shinohara, Toshimichi

    2014-07-01

    Age-related cataracts are a leading cause of blindness. Previously, we have demonstrated the association of the unfolded protein response with various cataractogenic stressors. However, DNA methylation alterations leading to suppression of lenticular antioxidant protection remains unclear. Here, we report the methylglyoxal-mediated sequential events responsible for Keap1 promoter DNA demethylation in human lens epithelial cells, because Keap1 is a negative regulatory protein that regulates the Nrf2 antioxidant protein. Methylglyoxal induces endoplasmic reticulum stress and activates the unfolded protein response leading to overproduction of reactive oxygen species before human lens epithelial cell death. Methylglyoxal also suppresses Nrf2 and DNA methyltransferases but activates the DNA demethylation pathway enzyme TET1. Bisulfite genomic DNA sequencing confirms the methylglyoxal-mediated Keap1 promoter DNA demethylation leading to overexpression of Keap1 mRNA and protein. Similarly, bisulfite genomic DNA sequencing shows that human clear lenses (n = 15) slowly lose 5-methylcytosine in the Keap1 promoter throughout life, at a rate of 1% per year. By contrast, diabetic cataractous lenses (n = 21) lose an average of 90% of the 5-methylcytosine regardless of age. Overexpressed Keap1 protein is responsible for decreasing Nrf2 by proteasomal degradation, thereby suppressing Nrf2-dependent stress protection. This study demonstrates for the first time the associations of unfolded protein response activation, Nrf2-dependent antioxidant system failure, and loss of Keap1 promoter methylation because of altered active and passive DNA demethylation pathway enzymes in human lens epithelial cells by methylglyoxal. As an outcome, the cellular redox balance is altered toward lens oxidation and cataract formation.

  17. An improved spinning lens test to determine the stiffness of the human lens

    PubMed Central

    Burd, H.J.; Wilde, G.S.; Judge, S.J.

    2011-01-01

    It is widely accepted that age-related changes in lens stiffness are significant for the development of presbyopia. However, precise details on the relative importance of age-related changes in the stiffness of the lens, in comparison with other potential mechanisms for the development of presbyopia, have not yet been established. One contributing factor to this uncertainty is the paucity and variability of experimental data on lens stiffness. The available published data generally indicate that stiffness varies spatially within the lens and that stiffness parameters tend to increase with age. However, considerable differences exist between these published data sets, both qualitatively and quantitatively. The current paper describes new and improved methods, based on the spinning lens approach pioneered by Fisher, R.F. (1971) ‘The elastic constants of the human lens’, Journal of Physiology, 212, 147–180, to make measurements on the stiffness of the human lens. These new procedures have been developed in an attempt to eliminate, or at least substantially reduce, various systematic errors in Fisher’s original experiment. An improved test rig has been constructed and a new modelling procedure for determining lens stiffness parameters from observations made during the test has been devised. The experiment involves mounting a human lens on a vertical rotor so that the lens spins on its optical axis (typically at 1000 rpm). An automatic imaging system is used to capture the outline of the lens, while it is rotating, at pre-determined angular orientations. These images are used to quantify the deformations developed in the lens as a consequence of the centripetal forces induced by the rotation. Lens stiffness is inferred using axisymmetric finite element inverse analysis in which a nearly-incompressible neo-Hookean constitutive model is used to represent the mechanics of the lens. A numerical optimisation procedure is used to determine the stiffness parameters

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

    PubMed

    Michael, R; Bron, A J

    2011-04-27

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

  19. Optical power of the isolated human crystalline lens

    PubMed Central

    Borja, David; Manns, Fabrice; Ho, Arthur; Ziebarth, Noel; Rosen, Alexandre M.; Jain, Rakhi; Amelinckx, Adriana; Arrieta, Esdras; Augusteyn, Robert C.; Parel, Jean-Marie

    2009-01-01

    Purpose To characterize the age-dependence of isolated human crystalline lens power and quantify the contributions of the lens surfaces and refractive index gradient. Methods Experiments were performed on a total of 100 eyes from 73 donors (average post-mortem: 2.8±1.6 days) with an age range of 6 to 94 years. Lens power was measured with a modified commercial lensmeter or with an optical system based on the Scheiner principle. The radius of curvature and asphericity of the isolated lens surfaces were measured by shadowphotography. For each lens the contributions of the surfaces and the refractive index gradient to the measured lens power were calculated using an optical ray tracing software. The age dependency of these refractive powers was assessed. Results The total refractive power and surface refractive power both showed a biphasic age dependency. The total power decreased at a rate of −0.41D/year between age 6 and 58.1, and increased at a rate of 0.33D/year between age 58.1 and 82. The surface contribution decreased at a rate of −0.13D/year between age 6 and 55.2, and increased at a rate of 0.04D/year between age 55.2 and 94. The relative contribution of the surfaces increased by 0.17%/year. The equivalent refractive index also showed a biphasic age dependency with a decrease at a rate of −3.9×10−4/year from age 6 to 60.4 followed by a plateau. Conclusions The lens power decreases with age due mainly to a decrease in the contribution of the gradient. The use of a constant equivalent refractive index value to calculate lens power using the lens maker formula will underestimate the power of young lenses and overestimate the power of older lenses. PMID:18316704

  20. N-epsilon-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins.

    PubMed Central

    Ahmed, M U; Brinkmann Frye, E; Degenhardt, T P; Thorpe, S R; Baynes, J W

    1997-01-01

    Advanced glycation end-products and glycoxidation products, such as Nepsilon-(carboxymethyl)lysine (CML) and pentosidine, accumulate in long-lived tissue proteins with age and are implicated in the aging of tissue proteins and in the development of pathology in diabetes, atherosclerosis and other diseases. In this paper we describe a new advanced glycation end-product, Nepsilon-(carboxyethyl)lysine (CEL), which is formed during the reaction of methylglyoxal with lysine residues in model compounds and in the proteins RNase and collagen. CEL was also detected in human lens proteins at a concentration similar to that of CML, and increased with age in parallel with the concentration of CML. Although CEL was formed in highest yields during the reaction of methylglyoxal and triose phosphates with lysine and protein, it was also formed in reactions of pentoses, ascorbate and other sugars with lysine and RNase. We propose that levels of CML and CEL and their ratio to one another in tissue proteins and in urine will provide an index of glyoxal and methylglyoxal concentrations in tissues, alterations in glutathione homoeostasis and dicarbonyl metabolism in disease, and sources of advanced glycation end-products in tissue proteins in aging and disease. PMID:9182719

  1. Dating the time of birth: A radiocarbon calibration curve for human eye-lens crystallines

    NASA Astrophysics Data System (ADS)

    Kjeldsen, Henrik; Heinemeier, Jan; Heegaard, Steffen; Jacobsen, Christina; Lynnerup, Niels

    2010-04-01

    Radiocarbon bomb-pulse dating has been used to measure the formation age of human eye-lens crystallines. Lens crystallines are special proteins in the eye-lens that consist of virtually inert tissue. The experimental data show that the radiocarbon ages to a large extent reflect the time of birth, in accordance with expectations. Moreover, it has been possible to develop an age model for the formation of the eye-lens crystallines. From this model a radiocarbon calibration curve for lens crystallines has been calculated. As a consequence, the time of birth of humans can be determined with an accuracy of a few years by radiocarbon dating.

  2. Method for quantifying optical properties of the human lens

    DOEpatents

    Loree, T.R.; Bigio, I.J.; Zuclich, J.A.; Shimada, Tsutomu; Strobl, K.

    1999-04-13

    A method is disclosed for quantifying optical properties of the human lens. The present invention includes the application of fiberoptic, OMA-based instrumentation as an in vivo diagnostic tool for the human ocular lens. Rapid, noninvasive and comprehensive assessment of the optical characteristics of a lens using very modest levels of exciting light are described. Typically, the backscatter and fluorescence spectra (from about 300- to 900-nm) elicited by each of several exciting wavelengths (from about 300- to 600-nm) are collected within a few seconds. The resulting optical signature of individual lenses is then used to assess the overall optical quality of the lens by comparing the results with a database of similar measurements obtained from a reference set of normal human lenses having various ages. Several metrics have been identified which gauge the optical quality of a given lens relative to the norm for the subject`s chronological age. These metrics may also serve to document accelerated optical aging and/or as early indicators of cataract or other disease processes. 8 figs.

  3. Method for quantifying optical properties of the human lens

    DOEpatents

    Loree, deceased, Thomas R.; Bigio, Irving J.; Zuclich, Joseph A.; Shimada, Tsutomu; Strobl, Karlheinz

    1999-01-01

    Method for quantifying optical properties of the human lens. The present invention includes the application of fiberoptic, OMA-based instrumentation as an in vivo diagnostic tool for the human ocular lens. Rapid, noninvasive and comprehensive assessment of the optical characteristics of a lens using very modest levels of exciting light are described. Typically, the backscatter and fluorescence spectra (from about 300- to 900-nm) elicited by each of several exciting wavelengths (from about 300- to 600-nm) are collected within a few seconds. The resulting optical signature of individual lenses is then used to assess the overall optical quality of the lens by comparing the results with a database of similar measurements obtained from a reference set of normal human lenses having various ages. Several metrics have been identified which gauge the optical quality of a given lens relative to the norm for the subject's chronological age. These metrics may also serve to document accelerated optical aging and/or as early indicators of cataract or other disease processes.

  4. No turnover in lens lipids for the entire human lifespan.

    PubMed

    Hughes, Jessica R; Levchenko, Vladimir A; Blanksby, Stephen J; Mitchell, Todd W; Williams, Alan; Truscott, Roger J W

    2015-03-11

    Lipids are critical to cellular function and it is generally accepted that lipid turnover is rapid and dysregulation in turnover results in disease (Dawidowicz 1987; Phillips et al., 2009; Liu et al., 2013). In this study, we present an intriguing counter-example by demonstrating that in the center of the human ocular lens, there is no lipid turnover in fiber cells during the entire human lifespan. This discovery, combined with prior demonstration of pronounced changes in the lens lipid composition over a lifetime (Hughes et al., 2012), suggests that some lipid classes break down in the body over several decades, whereas others are stable. Such substantial changes in lens cell membranes may play a role in the genesis of age-related eye disorders. Whether long-lived lipids are present in other tissues is not yet known, but this may prove to be important in understanding the development of age-related diseases.

  5. Nanoceria have no genotoxic effect on human lens epithelial cells

    NASA Astrophysics Data System (ADS)

    Pierscionek, Barbara K.; Li, Yuebin; Yasseen, Akeel A.; Colhoun, Liza M.; Schachar, Ronald A.; Chen, Wei

    2010-01-01

    There are no treatments for reversing or halting cataract, a disease of the structural proteins in the eye lens, that has associations with other age-related degenerative conditions such as Alzheimer's disease. The incidence of cataract and associated conditions is increasing as the average age of the population rises. Protein folding diseases are difficult to assess in vivo as proteins and their age-related changes are assessed after extraction. Nanotechnology can be used to investigate protein changes in the intact lens as well as for a potential means of drug delivery. Nanoparticles, such as cerium oxide (CeO2) which have antioxidant properties, may even be used as a means of treating cataract directly. Prior to use in treatments, nanoparticle genotoxicity must be tested to assess the extent of any DNA or chromosomal damage. Sister chromatid exchanges were measured and DNA damage investigated using the alkaline COMET assay on cultured human lens epithelial cells, exposed to 5 and 10 µg ml-1 of CeO2 nanoparticles (nanoceria). Nanoceria at these dosages did not cause any DNA damage or significant increases in the number of sister chromatid exchanges. The absence of genotoxic effects on lens cells suggests that nanoceria, in the doses and exposures tested in this study, are not deleterious to the eye lens and have the potential for use in studying structural alterations, in developing non-surgical cataract treatments and in investigating other protein folding diseases.

  6. Shear modulus data for the human lens determined from a spinning lens test.

    PubMed

    Wilde, G S; Burd, H J; Judge, S J

    2012-04-01

    The paper describes a program of mechanical testing on donated human eye bank lenses. The principal purpose of the tests was to obtain experimental data on the shear modulus of the lens for use in future computational models of the accommodation process. Testing was conducted using a procedure in which deformations are induced in the lens by spinning it about its polar axis. Shear modulus data were inferred from these observed deformations by means of a finite element inverse analysis procedure in which the spatial variation of the shear modulus within the lens is represented by an appropriate function (see Burd et al., 2011 for a detailed specification of the design of the spinning lens test rig, experimental protocols and associated data analysis procedures that were employed in the tests). Inferred data on lens shear modulus are presented for a set of twenty-nine lenses in the age range 12 years to 58 years. The lenses were tested between 47 h and 110 h from the time of death (average post-mortem time 74 h). Care was taken to exclude any lenses that had been affected by excessive post-mortem swelling, or any lenses that had suffered mechanical damage during storage, transit or the testing process. The experimental data on shear modulus indicate that, for young lenses, the cortex is stiffer than the nucleus. The shear modulus of the nucleus and cortex both increase with increasing age. The shear modulus of the nucleus increases more rapidly than the cortex with the consequence that from an age of about 45 years onwards the nucleus is stiffer than the cortex. The principal shear modulus data presented in the paper were obtained by testing at a rotational speed of 1,000 rpm. Supplementary tests were conducted at rotational speeds of 700 rpm and 1,400 rpm. The results from these supplementary tests are in good agreement with the data obtained from the principal 1,000 rpm tests. Studies on the possible effects of lens drying during the test suggested that this factor

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

    PubMed Central

    Sheil, Conor J.; Goncharov, Alexander V.

    2016-01-01

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

  8. No turnover in lens lipids for the entire human lifespan

    PubMed Central

    Hughes, Jessica R; Levchenko, Vladimir A; Blanksby, Stephen J; Mitchell, Todd W; Williams, Alan; Truscott, Roger JW

    2015-01-01

    Lipids are critical to cellular function and it is generally accepted that lipid turnover is rapid and dysregulation in turnover results in disease (Dawidowicz 1987; Phillips et al., 2009; Liu et al., 2013). In this study, we present an intriguing counter-example by demonstrating that in the center of the human ocular lens, there is no lipid turnover in fiber cells during the entire human lifespan. This discovery, combined with prior demonstration of pronounced changes in the lens lipid composition over a lifetime (Hughes et al., 2012), suggests that some lipid classes break down in the body over several decades, whereas others are stable. Such substantial changes in lens cell membranes may play a role in the genesis of age-related eye disorders. Whether long-lived lipids are present in other tissues is not yet known, but this may prove to be important in understanding the development of age-related diseases. DOI: http://dx.doi.org/10.7554/eLife.06003.001 PMID:25760082

  9. Binocular Lens Treatment in Tree Shrews: Effect of Age and Comparison of Plus Lens Wear with Recovery from Minus Lens-induced Myopia

    PubMed Central

    Siegwart, John T.; Norton, Thomas T.

    2010-01-01

    the lens in place). Minus-lens wear in both the young and juvenile groups, which initially made eyes more hyperopic, consistently produced compensation to the minus lens so that eyes reached age-appropriate refractions while wearing the lenses. When the minus lenses were removed, the eyes recovered quickly to age-matched normal values. The consistent recovery response from myopia in juvenile eyes after minus-lens compensation, compared with the highly variable response to plus lens wear in age-matched juvenile animals suggests that eyes retain the ability to detect the myopic refractive state, but there is an age-related decrease in the ability of normal eyes to use myopia to slow their elongation rate below normal. If juvenile human eyes, compared with infants, have a similar difficulty in using myopia to slow axial elongation, this may contribute to myopia development, especially in eyes with a genetic pre-disposition to elongate. PMID:20713041

  10. Binocular lens treatment in tree shrews: Effect of age and comparison of plus lens wear with recovery from minus lens-induced myopia.

    PubMed

    Siegwart, John T; Norton, Thomas T

    2010-11-01

    ). Minus-lens wear in both the young and juvenile groups, which initially made eyes more hyperopic, consistently produced compensation to the minus lens so that eyes reached age-appropriate refractions while wearing the lenses. When the minus lenses were removed, the eyes recovered quickly to age-matched normal values. The consistent recovery response from myopia in juvenile eyes after minus-lens compensation, compared with the highly variable response to plus lens wear in age-matched juvenile animals suggests that eyes retain the ability to detect the myopic refractive state, but there is an age-related decrease in the ability of normal eyes to use myopia to slow their elongation rate below normal. If juvenile human eyes, compared with infants, have a similar difficulty in using myopia to slow axial elongation, this may contribute to myopia development, especially in eyes with a genetic pre-disposition to elongate.

  11. Spatial distributions of glutathione and its endogenous conjugates in normal bovine lens and a model of lens aging.

    PubMed

    Nye-Wood, Mitchell G; Spraggins, Jeffrey M; Caprioli, Richard M; Schey, Kevin L; Donaldson, Paul J; Grey, Angus C

    2016-11-09

    Glutathione (GSH) is the archetypal antioxidant, and plays a central role in the protection of the ocular lens from cataract formation. High levels of GSH are maintained in the transparent lens, but with advancing age, GSH levels fall in the lens nucleus relative to outer cortical cells, thereby exposing the nucleus of the lens to the damaging effects of oxygen radicals, which ultimately leads to age-related nuclear (ARN) cataract. Under normal conditions, GSH also forms endogenous conjugates to detoxify the lens of reactive cellular metabolites and to maintain cell homeostasis. Due to the intrinsic gradient of lens fibre cell age, the lens contains distinct regions with different metabolic requirements for GSH. To investigate the impact of fibre cell and lens aging on the varied roles that GSH plays in the lens, we have utilised high mass resolution MALDI mass spectrometry profiling and imaging analysis of lens tissue sections. High Dynamic Range (HDR)-MALDI FTICR mass spectrometry was used as an initial screening method to detect regional differences in lens metabolites from normal bovine lenses and in those subjected to hyperbaric oxygen as a model of lens aging. Subsequent MALDI imaging analysis was used to spatially map GSH and its endogenous conjugates throughout all lenses. Accurate mass measurement by MALDI FTICR analysis and LC-MS/MS mass spectrometry of lens region homogenates were subsequently used to identify endogenous GSH conjugates. While the distribution and relative abundance of GSH-related metabolic intermediates involved in detoxification pathways remained relatively unchanged upon HBO treatment, those involved in its antioxidant function were altered under conditions of oxidative stress. For example, reduced glutathione levels were decreased in the lens cortex while oxidised glutathione levels were elevated in the lens outer cortex upon HBO treatment. Interestingly, cysteineglutathione disulfide, was detected in the inner cortex of the normal

  12. Spatial distribution of metabolites in the human lens.

    PubMed

    Tamara, Semen O; Yanshole, Lyudmila V; Yanshole, Vadim V; Fursova, Anjella Zh; Stepakov, Denis A; Novoselov, Vladimir P; Tsentalovich, Yuri P

    2016-02-01

    Spatial distribution of 34 metabolites along the optical and equatorial axes of the human lens has been determined. For the majority of metabolites, the homogeneous distribution has been observed. That suggests that the rate of the metabolite transformation in the lens is low due to the general metabolic passivity of the lens fiber cells. However, the redox processes are active in the lens; as a result, some metabolites, including antioxidants, demonstrate the "nucleus-depleted" type of distribution, whereas secondary UV filters show the "nucleus-enriched" type. The metabolite concentrations at the lens poles and equator are similar for all metabolites under study. The concentric pattern of the "nucleus-depleted" and "nucleus-enriched" distributions testifies that the metabolite distribution inside the lens is mostly governed by a passive diffusion, relatively free along the fiber cells and retarded in the radial direction across the cells. No significant difference in the metabolite distribution between the normal and cataractous human lenses was found.

  13. The concentration of light in the human lens.

    PubMed Central

    Merriam, J C

    1996-01-01

    PURPOSE: This thesis explores the idea that light energy, especially ultraviolet light, contributes to the unequal distribution of cataract around the world and to the development of cortical opacities. METHODS: In the first section, the thesis reviews historical concepts of the function of the lens and the nature of cataract, epidemiologic data on the global distribution of cataract, and clinical observations of the predominant location of cortical opacification. Second, computer ray tracings and geometric optics demonstrate the passage of light of varying angle of incidence within the lens. Third, two models of the human eye are used to study the refraction of light by the cornea and lens and illustrate the concentration of energy at the equatorial plane of the lens. RESULTS: Cataract prevalence increases with proximity to the earth's equator, and cortical cataract is most common in the inferior and inferonasal lens. Theoretical studies and the eye models both demonstrate that the concentration of light within the lens increases with angle of incidence, and the eye models suggest that the inferior and inferonasal lens receives significantly more energy than other sections of the lens. CONCLUSION: The prevalence of cataract and exposure to ultraviolet energy both increase with decreasing latitude. The most common location of cortical cataract in the inferonasal lens is consistent with the greater dose of light energy received by this portion of the lens. These studies suggest that the global distribution of cataract and the development of cortical cataract are at least in part dependent on the dose of ultraviolet light received by the lens. Images FIGURE 1 FIGURE 2 FIGURE 27 FIGURE 28 FIGURE 29 FIGURE 31 FIGURE 32 FIGURE 33 FIGURE 34 FIGURE 36 FIGURE 37 FIGURE 38 FIGURE 50 FIGURE 51 FIGURE 52 FIGURE 53 FIGURE 54 FIGURE 56 FIGURE 60 FIGURE 61 FIGURE 63 FIGURE 64 FIGURE 65 FIGURE 68 FIGURE 69 FIGURE 70 FIGURE 71 PMID:8981716

  14. MALDI-MS-imaging of whole human lens capsule.

    PubMed

    Ronci, Maurizio; Sharma, Shiwani; Chataway, Tim; Burdon, Kathryn P; Martin, Sarah; Craig, Jamie E; Voelcker, Nicolas H

    2011-08-05

    The ocular lens capsule is a smooth, transparent basement membrane that encapsulates the lens and is composed of a rigid network of interacting structural proteins and glycosaminoglycans. During cataract surgery, the anterior lens capsule is routinely removed in the form of a circular disk. We considered that the excised capsule could be easily prepared for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-MSI) analysis. MALDI-MSI is a powerful tool to elucidate the spatial distribution of small molecules, peptides, and proteins within tissues. Here, we apply this molecular imaging technique to analyze the freshly excised human lens capsule en face. We demonstrate that novel information about the distribution of proteins by MALDI-MSI can be obtained from this highly compact connective tissue, having no evident histo-morphological characteristics. Trypsin digestion carried out on-tissue is shown to improve MALDI-MSI analysis of human lens capsules and affords high repeatability. Most importantly, MALDI-MSI analysis reveals a concentric distribution pattern of proteins such as apolipoprotein E (ApoE) and collagen IV alpha-1 on the anterior surface of surgically removed lens capsule, which may indicate direct or indirect effects of environmental and mechanical stresses on the human ocular lens.

  15. Proteomics and Phosphoproteomics Analysis of Human Lens Fiber Cell Membranes

    PubMed Central

    Wang, Zhen; Han, Jun; David, Larry L.; Schey, Kevin L.

    2013-01-01

    Purpose. The human lens fiber cell insoluble membrane fraction contains important membrane proteins, cytoskeletal proteins, and cytosolic proteins that are strongly associated with the membrane. The purpose of this study was to characterize the lens fiber cell membrane proteome and phosphoproteome from human lenses. Methods. HPLC-mass spectrometry–based multidimensional protein identification technology (MudPIT), without or with phosphopeptide enrichment, was applied to study the proteome and phosphoproteome of lens fiber cell membranes, respectively. Results. In total, 951 proteins were identified, including 379 integral membrane and membrane-associated proteins. Enriched gene categories and pathways based on the proteomic analysis include carbohydrate metabolism (glycolysis/gluconeogenesis, pentose phosphate pathway, pyruvate metabolism), proteasome, cell-cell signaling and communication (GTP binding, gap junction, focal adhesion), glutathione metabolism, and actin regulation. The combination of TiO2 phosphopeptide enrichment and MudPIT analysis revealed 855 phosphorylation sites on 271 proteins, including 455 phosphorylation sites that have not been previously identified. PKA, PKC, CKII, p38MAPK, and RSK are predicted as the major kinases for phosphorylation on the sites identified in the human lens membrane fraction. Conclusions. The results presented herein significantly expand the characterized proteome and phosphoproteome of the human lens fiber cell and provide a valuable reference for future research in studies of lens development and disease. PMID:23349431

  16. Dynamic optometer. [for electronic recording of human lens anterior surface

    NASA Technical Reports Server (NTRS)

    Wilson, D. C.

    1974-01-01

    A dynamic optometer that electronically records the position of the anterior surface of the human lens is described. The geometrical optics of the eye and optometer, and the scattering of light from the lens, are closely examined to determine the optimum conditions for adjustment of the instrument. The light detector and associated electronics are also considered, and the operating conditions for obtaining the best signal-to-noise ratio are determined.

  17. The effect of paraformaldehyde fixation and PBS storage on the water content of the human lens

    PubMed Central

    Willekens, Ben

    2008-01-01

    Purpose Fixation and phosphate buffered saline (PBS) storage are frequently used before studies of the morphological, biochemical, and optical properties of the human lens begin. It is assumed that this does not alter the properties being examined. The present study was undertaken to determine the effects of fixation and PBS storage on the human lens wet weight. Methods Human donor lenses were incubated in a buffered paraformaldehyde (PF) solution or in PBS and their wet weights were monitored for up to 44 and 13 days, respectively. Results PF fixation resulted in a large decrease in wet weight, averaging 25%±2.3% at 30 days for 14 human donor lenses, aged 49–80 years. The loss was essentially complete by 21 days. Out of the 10 lenses, aged 52–71 years, which were incubated in PBS alone, six of them increased in weight by an average of 38% over 13 days and four ruptured within four days. Comparison of literature data for a fixed eight-year-old lens with those for an unfixed seven-year-old lens indicated that the decrease in wet weight was due mainly to a loss of water from the cortex, which resulted in virtual disappearance of the water/protein gradient and the formation of a plateau containing 58% water in over 90% of the lens. Conclusions Fixation substantially alters the amount and distribution of water in the human lens. Caution should be exercised when interpreting data on water and protein distributions as well as cell dimensions obtained with lenses which have been fixed. In addition, prolonged storage of a lens in PBS will result in substantial water uptake, which may affect measurements of their dimensions and optical properties. PMID:18253098

  18. Flavin nucleotides in human lens: regional distribution in brunescent cataracts.

    PubMed

    Bhat, K S; Nayak, S

    1998-12-01

    The biochemical mechanism(s) underlying brunescent cataracts remain unclear. Oxidative stress due to reactive oxygen species may have a role in the pigmentation process in eye lens. We have analysed human cataractous lenses for flavins by high-performance liquid chromatography (HPLC), since flavins are light sensitive and act as endogenous sensitizers generating reactive oxygen species in the eye. The most significant observation in this study is that higher levels of flavin nucleotides occur in brown lens compared to yellow lens. The concentration of flavin nucleotides (flavin monouncleotide, FMN + flavin adenine dinucleotide, FAD) was highest in the nuclear region of the lens followed by the cortical and capsule-epithelial regions. However, the ratio of FAD/FMN was lowest in the nuclear region of the lens followed by other regions. On the other hand, riboflavin was not detected in any of the lens (cataractous) regions. These results suggest that the observed increase in flavin nucleotides in the ocular tissue could contribute towards deepening of lens pigmentation.

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

    PubMed Central

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

    2012-01-01

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

  20. The eye lens: age-related trends and individual variations in refractive index and shape parameters

    PubMed Central

    Pierscionek, Barbara; Bahrami, Mehdi; Hoshino, Masato; Uesugi, Kentaro; Regini, Justyn; Yagi, Naoto

    2015-01-01

    The eye lens grows throughout life by cell accrual on its surface and can change shape to adjust the focussing power of the eye. Varying concentrations of proteins in successive cell layers create a refractive index gradient. The continued growth of the lens and age-related changes in proteins render it less able to alter shape with loss of capacity by the end of the sixth decade of life. Growth and protein ageing alter the refractive index but as accurate measurement of this parameter is difficult, the nature of such alterations remains uncertain. The most accurate method to date for measuring refractive index in intact lenses has been developed at the SPring-8 synchrotron. The technique, based on Talbot interferometry, has an X-ray source and was used to measure refractive index in sixty-six human lenses, aged from 16 to 91 years. Height and width were measured for forty-five lenses. Refractive index contours show decentration in some older lenses but individual variations mask age-related trends. Refractive index profiles along the optic axis have relatively flat central sections with distinct micro-fluctuations and a steep gradient in the cortex but do not exhibit an age-related trend. The refractive index profiles in the equatorial aspect show statistical significance with age, particularly for lenses below the age of sixty that had capacity to alter shape in vivo. The maximum refractive index in the lens centre decreases slightly with age with considerable scatter in the data and there are age-related variations in sagittal thickness and equatorial height. PMID:26416418

  1. ACCOMMODATIVE MOVEMENTS OF THE LENS/CAPSULE AND THE STRAND THAT EXTENDS BETWEEN THE POSTERIOR VITREOUS ZONULE INSERTION ZONE & THE LENS EQUATOR, IN RELATION TO THE VITREOUS FACE AND AGING

    PubMed Central

    CROFT, MARY ANN; HEATLEY, GREGG; MCDONALD, JARED P.; KATZ, ALEXANDER; KAUFMAN, PAUL L.

    2016-01-01

    Purpose To elucidate the dynamic accommodative movements of the lens capsule, posterior lens and the strand that attaches to the posterior vitreous zonule insertion zone and posterior lens equator (PVZ INS-LE), and their age-related changes. Methods Twelve human subjects (ages 19–65 years) and twelve rhesus monkeys (ages 6–27 years) were studied. Accommodation was induced pharmacologically (humans) or by central electrical stimulation (monkeys). Ultrasound biomicroscopy was used to image intraocular structures in both species. Surgical procedures and contrast agents were utilized in the monkey eyes to elucidate function and allow visualization of the intraocular accommodative structures. Results Human: The posterior pole of the lens moves posteriorly during accommodation in proportion to accommodative amplitude and ciliary muscle movement. Monkey: Similar accommodative movements of the posterior lens pole were seen in the monkey eyes. Following extracapsular lens extraction (ECLE), the central capsule bows backward during accommodation in proportion to accommodative amplitude and ciliary muscle movement, while the peripheral capsule moves forward. During accommodation the ciliary muscle moved forward by ~1.0 mm, pulling forward the vitreous zonule and the PVZ INS-LE structure. During the accommodative response the PVZ INS-LE structure moved forward when the lens was intact and when the lens substance and capsule were removed. In both the monkey and the human eyes these movements declined with age. Conclusions The accommodative shape change of the central capsule may be due to the elastic properties of the capsule itself. For these capsule/lens accommodative posterior movements to occur, the vitreous face must either allow for it or facilitate it. The PVZ INS-LE structure may act as a “strut” to the posterior lens equator (pushing the lens equator forward) and thereby facilitate accommodative forward lens equator movement and lens thickening. The age

  2. Somatic Variants in the Human Lens Epithelium: A Preliminary Assessment

    PubMed Central

    Mesa, Rosana; Tyagi, Manoj; Harocopos, George; Vollman, David; Bassnett, Steven

    2016-01-01

    Purpose We hypothesize that somatic mutations accumulate in cells of the human lens and may contribute to the development of cortical or posterior sub-capsular cataracts. Here, we used a Next-generation sequencing (NGS) strategy to screen for low-allelic frequency variants in DNA extracted from human lens epithelial samples. Methods Next-Generation sequencing of 151 cancer-related genes (WUCaMP2 panel) was performed on DNA extracted from post-mortem or surgical specimens obtained from 24 individuals. Usually, pairwise comparisons were made between two or more ocular samples from the same individual, allowing putative somatic variants detected in lens samples to be differentiated from germline variants. Results Use of a targeted hybridization approach enabled high sequence coverage (>1000-fold) of the WUCaMP2 genes. In addition to high-frequency variants (corresponding to homozygous or heterozygous SNPs and Indels), somatic variants with allelic frequencies of 1-4% were detected in the lens epithelial samples. The presence of one such variant, a T > C point substitution at position 32907082 in BRCA2, was verified subsequently using droplet digital PCR. Conclusions Low-allelic fraction variants are present in the human lens epithelium, at frequencies consistent with the presence of millimeter-sized clones. PMID:27537255

  3. LENS: web-based lens for enrichment and network studies of human proteins

    PubMed Central

    2015-01-01

    Background Network analysis is a common approach for the study of genetic view of diseases and biological pathways. Typically, when a set of genes are identified to be of interest in relation to a disease, say through a genome wide association study (GWAS) or a different gene expression study, these genes are typically analyzed in the context of their protein-protein interaction (PPI) networks. Further analysis is carried out to compute the enrichment of known pathways and disease-associations in the network. Having tools for such analysis at the fingertips of biologists without the requirement for computer programming or curation of data would accelerate the characterization of genes of interest. Currently available tools do not integrate network and enrichment analysis and their visualizations, and most of them present results in formats not most conducive to human cognition. Results We developed the tool Lens for Enrichment and Network Studies of human proteins (LENS) that performs network and pathway and diseases enrichment analyses on genes of interest to users. The tool creates a visualization of the network, provides easy to read statistics on network connectivity, and displays Venn diagrams with statistical significance values of the network's association with drugs, diseases, pathways, and GWASs. We used the tool to analyze gene sets related to craniofacial development, autism, and schizophrenia. Conclusion LENS is a web-based tool that does not require and download or plugins to use. The tool is free and does not require login for use, and is available at http://severus.dbmi.pitt.edu/LENS. PMID:26680011

  4. Design and analysis of an adaptive lens that mimics the performance of the crystalline lens in the human eye

    NASA Astrophysics Data System (ADS)

    Santiago-Alvarado, Agustin; Cruz-Félix, Angel S.; Iturbide-Jiménez, F.; Martínez-López, M.; Ramírez-Como, M.; Armengol-Cruz, V.; Vásquez-Báez, I.

    2014-09-01

    Tunable lenses are optical systems that have attracted much attention due to their potential applications in such areas like ophthalmology, machine vision, microscopy and laser processing. In recent years we have been working in the analysis and performance of a liquid-filled variable focal length lens, this is a lens that can modify its focal length by changing the amount of water within it. Nowadays we extend our study to a particular adaptive lens known as solid elastic lens (SEL) that it is formed by an elastic main body made of Polydimethylsiloxane (PDMS Sylgard 184). In this work, we present the design, simulation and analysis of an adaptive solid elastic lens that in principle imitates the accommodation process of the crystalline lens in the human eye. For this work, we have adopted the parameters of the schematic eye model developed in 1985 by Navarro et al.; this model represents the anatomy of the eye as close as possible to reality by predicting an acceptable and accurate quantity of spherical and chromatic aberrations without any shape fitting. An opto-mechanical analysis of the accommodation process of the adaptive lens is presented, by simulating a certain amount of radial force applied onto the SEL using the finite element method with the commercial software SolidWorks®. We also present ray-trace diagrams of the simulated compression process of the adaptive lens using the commercial software OSLO®.

  5. A longitudinal study assessing lens thickness changes in the eye of the growing beagle using ultrasound scanning: relevance to age of dogs in regulatory toxicology studies.

    PubMed

    Maynard, Juliana; Sykes, Angela; Powell, Helen; Healing, Guy; Scott, Marietta; Holmes, Andrew; Ricketts, Sally-Ann; Stewart, Jane; Davis, Stewart

    2014-12-01

    The lens is formed in utero with new secondary lens fibres added as outer layers throughout life in a growth pattern characteristic of the species. This study examined the time course of beagle lens growth to better understand the optimal starting age of dogs for safety studies to support adult versus paediatric indications, and to assess the feasibility of non-invasively monitoring lens growth with high frequency ultrasound. Ultrasound scanning was performed in six female beagle dogs using the Vevo770. All dogs were imaged in B-mode using local anaesthetic but without sedation. Imaging was carried out every 2 weeks from 8 to 22 weeks of age and then monthly until 62 weeks of age. The dogs tolerated the procedure well. The lens was visible in all dogs and measuring the lens thickness with high frequency ultrasound demonstrated good analytical reproducibility [Root Mean Square (RMS) = 3.13%]. No differences between the left and right eye existed and lens thickness correlated with body weight. The highest weekly growth rate was before 12 weeks of age. A statistically significant difference between monthly thickness was detected until 42 weeks of age at which point growth reached a plateau. During the experiment, lenses grew by 29.7% reaching an average thickness of 6.4 mm ± 0.03. By 10 months of age (the typical age used for routine toxicological evaluation), beagles have reached a plateau in lens growth that is analogous to human adults. Where lens is a target organ of concern it is suggested that beagles under 6 months old may be a better model for determining paediatric safety.

  6. On the growth and internal structure of the human lens.

    PubMed

    Augusteyn, Robert C

    2010-06-01

    Growth of the human lens and the development of its internal features are examined using in vivo and in vitro observations on dimensions, weights, cell sizes, protein gradients and other properties. In vitro studies have shown that human lens growth is biphasic, asymptotic until just after birth and linear for most of postnatal life. This generates two distinct compartments, the prenatal and the postnatal. The prenatal growth mode leads to the formation of an adult nuclear core of fixed dimensions and the postnatal, to an ever-expanding cortex. The nuclear core and the cortex have different properties and can readily be physically separated. Communication and adhesion between the compartments is poor in older lenses. In vivo slit lamp examination reveals several zones of optical discontinuity in the lens. Different nomenclatures have been used to describe these, with the most common recognizing the embryonic, foetal, juvenile and adult nuclei as well as the cortex and outer cortex. Implicit in this nomenclature is the idea that the nuclear zones were generated at defined periods of development and growth. This review examines the relationship between the two compartments observed in vitro and the internal structures revealed by slit lamp photography. Defining the relationship is not as simple as it might seem because of remodeling and cell compaction which take place, mostly in the first 20 years of postnatal life. In addition, different investigators use different nomenclatures when describing the same regions of the lens. From a consideration of the dimensions, the dry mass contents and the protein distributions in the lens and in the various zones, it can be concluded that the juvenile nucleus and the layers contained within it, as well as most of the adult nucleus, were actually produced during prenatal life and the adult nucleus was completed within 3 months after birth, in the final stages of the prenatal growth mode. Further postnatal growth takes place

  7. On the growth and internal structure of the human lens

    PubMed Central

    Augusteyn, Robert C

    2010-01-01

    Growth of the human lens and the development of its internal features are examined using in vivo and in vitro observations on dimensions, weights, cell sizes, protein gradients and other properties. In vitro studies have shown that human lens growth is biphasic, asymptotic until just after birth and linear for most of postnatal life. This generates two distinct compartments, the prenatal and the postnatal. The prenatal growth mode leads to the formation of an adult nuclear core of fixed dimensions and the postnatal, to an ever-expanding cortex. The nuclear core and the cortex have different properties and can readily be physically separated. Communication and adhesion between the compartments is poor in older lenses. In vivo slit lamp examination reveals several zones of optical discontinuity in the lens. Different nomenclatures have been used to describe these, with the most common recognizing the embryonic, foetal, juvenile and adult nuclei as well as the cortex and outer cortex. Implicit in this nomenclature is the idea that the nuclear zones were generated at defined periods of development and growth. This review examines the relationship between the two compartments observed in vitro and the internal structures revealed by slit lamp photography. Defining the relationship is not as simple as it might seem because of remodeling and cell compaction which take place, mostly in the first 20 years of postnatal life. In addition, different investigators use different nomenclatures when describing the same regions of the lens. From a consideration of the dimensions, the dry mass contents and the protein distributions in the lens and in the various zones, it can be concluded that the juvenile nucleus and the layers contained within it, as well as most of the adult nucleus, were actually produced during prenatal life and the adult nucleus was completed within 3 months after birth, in the final stages of the prenatal growth mode. Further postnatal growth takes place

  8. Lipid-protein interactions in plasma membranes of fiber cells isolated from the human eye lens.

    PubMed

    Raguz, Marija; Mainali, Laxman; O'Brien, William J; Subczynski, Witold K

    2014-03-01

    The protein content in human lens membranes is extremely high, increases with age, and is higher in the nucleus as compared with the cortex, which should strongly affect the organization and properties of the lipid bilayer portion of intact membranes. To assess these effects, the intact cortical and nuclear fiber cell plasma membranes isolated from human lenses from 41- to 60-year-old donors were studied using electron paramagnetic resonance spin-labeling methods. Results were compared with those obtained for lens lipid membranes prepared from total lipid extracts from human eyes of the same age group [Mainali, L., Raguz, M., O'Brien, W. J., and Subczynski, W. K. (2013) Biochim. Biophys. Acta]. Differences were considered to be mainly due to the effect of membrane proteins. The lipid-bilayer portions of intact membranes were significantly less fluid than lipid bilayers of lens lipid membranes, prepared without proteins. The intact membranes were found to contain three distinct lipid environments termed the bulk lipid domain, boundary lipid domain, and trapped lipid domain. However, the cholesterol bilayer domain, which was detected in cortical and nuclear lens lipid membranes, was not detected in intact membranes. The relative amounts of bulk and trapped lipids were evaluated. The amount of lipids in domains uniquely formed due to the presence of membrane proteins was greater in nuclear membranes than in cortical membranes. Thus, it is evident that the rigidity of nuclear membranes is greater than that of cortical membranes. Also the permeability coefficients for oxygen measured in domains of nuclear membranes were significantly lower than appropriate coefficients measured in cortical membranes. Relationships between the organization of lipids into lipid domains in fiber cells plasma membranes and the organization of membrane proteins are discussed.

  9. Lipid-Protein Interactions in Plasma Membranes of Fiber Cells Isolated from the Human Eye Lens

    PubMed Central

    Raguz, Marija; Mainali, Laxman; O’Brien, William J.; Subczynski, Witold K.

    2014-01-01

    The protein content in human lens membranes is extremely high, increases with age, and is higher in the nucleus as compared with the cortex, which should strongly affect the organization and properties of the lipid bilayer portion of intact membranes. To assess these effects, the intact cortical and nuclear fiber cell plasma membranes isolated from human lenses from 41- to 60-year-old donors were studied using electron paramagnetic resonance spin-labeling methods. Results were compared with those obtained for lens lipid membranes prepared from total lipid extracts from human eyes of the same age group [Mainali,L., Raguz, M., O’Brien, W. J., and Subczynski, W. K. (2013) Biochim. Biophys. Acta]. Differences were considered to be mainly due to the effect of membrane proteins. The lipid-bilayer portions of intact membranes were significantly less fluid than lipid bilayers of lens lipid membranes, prepared without proteins. The intact membranes were found to contain three distinct lipid environments termed the bulk lipid domain, boundary lipid domain, and trapped lipid domain. However, the cholesterol bilayer domain, which was detected in cortical and nuclear lens lipid membranes, was not detected in intact membranes. The relative amounts of bulk and trapped lipids were evaluated. The amount of lipids in domains uniquely formed due to the presence of membrane proteins was greater in nuclear membranes than in cortical membranes. Thus, it is evident that the rigidity of nuclear membranes is greater than that of cortical membranes. Also the permeability coefficients for oxygen measured in domains of nuclear membranes were significantly lower than appropriate coefficients measured in cortical membranes. Relationships between the organization of lipids into lipid domains in fiber cells plasma membranes and the organization of membrane proteins are discussed. PMID:24486794

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

    PubMed

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

    2015-12-01

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

  11. Innovative Troxler-free measurement of macular pigment and lens density with correction of the former for the aging lens.

    PubMed

    Bone, Richard A; Mukherjee, Anirbaan

    2013-10-01

    Simplified measurement of macular pigment optical density (MPOD) is important because of the ocular health benefits that are attributed to these retinal carotenoids. Here, we describe a novel instrument designed for this purpose, based on heterochromatic flicker photometry (HFP), which removes a number of difficulties that subjects often experience with traditional HFP. The instrument generates 1.5- and 15-deg diameter, centrally viewed stimuli that alternate between blue and green colors generated by light emitting diodes (LED). The 15 deg stimulus replaces the small, eccentrically viewed stimulus used in traditional HFP. Subjects adjust the blue LED intensity until flicker is eliminated in the case of the 1.5 deg stimulus and eliminated around the periphery in the case of the 15 deg stimulus. A microprocessor computes the subject's MPOD, in addition to the lens OD, and uses the latter to correct the MPOD. Good repeatability was confirmed through test-retest measurements on 52 subjects. The overwhelming majority of them stated that they found the test easy. The importance of the lens correction on MPOD measurements was confirmed in a simulation study. The study showed that, without the correction, MPOD would show an apparent age-related decline in a population for whom there was no real age dependence.

  12. 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?

  13. Soluble ascorbate free radical reductase in the human lens.

    PubMed

    Bando, M; Obazawa, H

    1994-01-01

    A major and a minor ascorbate free radical (AFR) reductase were separated from the soluble fraction in the human lens cortex by DEAE-cellulose ion-exchange column chromatography. These AFR reductases also exhibited diaphorase activity using dichlorophenolindophenol and ferricyanide as electron acceptors. The major AFR reductase was partially purified by 5'AMP-Sepharose 4B affinity column chromatography. This partially purified AFR reductase showed a single band of diaphorase activity in native polyacrylamide disc gel electrophoresis. This activity band corresponded to the major protein observed in protein staining by Coomassie Brilliant Blue. However, the protein staining by Coomassie Brilliant Blue showed this activity band surrounded by diffused staining. Molecular weight of the partially purified AFR reductase was determined to be 32 kDa by gel filtration, and the apparent Km value for AFR was about 15 microM. This major lens AFR reductase could be distinguished from soluble Neurospora, Euglena and cucumber AFR reductases, and from two ubiquitous enzymes with reduction activity of AFR and/or foreign compounds, ie, NADH-cytochrome b5 reductase and DT-diaphorase, by their molecular weights, Km values and/or ion-exchange chromatographic behaviors.

  14. Acid phosphatase and lipid peroxidation in human cataractous lens epithelium.

    PubMed

    Vasavada, A R; Thampi, P; Yadav, S; Rawal, U M

    1993-12-01

    The anterior lens epithelial cells undergo a variety of degenerative and proliferative changes during cataract formation. Acid phosphatase is primarily responsible for tissue regeneration and tissue repair. The lipid hydroperoxides that are obtained by lipid peroxidation of polysaturated or unsaturated fatty acids bring about deterioration of biological membranes at cellular and tissue levels. Acid phosphatase and lipid peroxidation activities were studied on the lens epithelial cells of nuclear cataract, posterior subcapsular cataract, mature cataract, and mixed cataract. Of these, mature cataractous lens epithelium showed maximum activity for acid phosphatase (516.83 moles of p-nitrophenol released/g lens epithelium) and maximum levels of lipid peroxidation (86.29 O.D./min/g lens epithelium). In contrast, mixed cataractous lens epithelium showed minimum activity of acid phosphatase (222.61 moles of p-nitrophenol released/g lens epithelium) and minimum levels of lipid peroxidation (54.23 O.D./min/g lens epithelium). From our study, we correlated the maximum activity of acid phosphatase in mature cataractous lens epithelium with the increased areas of superimposed cells associated with the formation of mature cataract. Likewise, the maximum levels of lipid peroxidation in mature cataractous lens epithelium was correlated with increased permeability of the plasma membrane. Conversely, the minimum levels of lipid peroxidation in mixed cataractous lens epithelium makes us presume that factors other than lipid peroxidation may also account for the formation of mixed type of cataract.

  15. Cost of Intraocular Lens vs. Contact Lens Treatment after Unilateral Congenital Cataract Surgery in the IATS at Age 5 Years

    PubMed Central

    Kruger, Stacey J.; DuBois, Lindreth; Becker, Edmund R.; Morrison, David; Wilson, Lorri; Wilson, M. Edward; Lambert, Scott R.

    2014-01-01

    Purpose To analyze differences in the cost of treatment for infants randomized to primary intraocular lens (IOL) implantation versus optical correction with a contact lens (CL) after unilateral cataract surgery in the Infant Aphakia Treatment Study (IATS). Design Retrospective cost analysis of a prospective, randomized clinical trial based on Georgia Medicaid reimbursement data as well as actual costs of supplies used during the study, adjusted for inflation. Participants The IATS is a multicenter (n=12) randomized, clinical trial comparing the optical treatment of aphakia with either primary IOL implantation (n=57) or CL correction (n=57) in 114 infants with unilateral congenital cataract. Intervention One hundred fourteen infants underwent unilateral cataract surgery and were either optically corrected by primary IOL implantation at the time of surgery or were corrected with a CL after surgery. Main Outcome Measures The mean cost of cataract surgery and all additional surgeries, examinations and supplies used up to 5 years of age. Results The 5-year treatment cost of an infant with a unilateral congenital cataract optically corrected with an IOL was $35,293 versus $33,452 for a patient treated with a CL after initial cataract surgery. The total cost of supplies was $2669 in the IOL group vs $6128 in the CL group. Conclusions Unilateral cataract surgery in infancy coupled with primary IOL implantation is about 5% more expensive than aphakia and CL correction. Patient costs are more than double with CL versus IOL. PMID:25439604

  16. Oxygen-induced changes in mitochondrial DNA and DNA repair enzymes in aging rat lens.

    PubMed

    Zhang, Yi; Ouyang, Shan; Zhang, Lan; Tang, Xianling; Song, Zhen; Liu, Ping

    2010-01-01

    The treatment of patients with hyperbaric oxygen (HBO), vitrectomy and loss of vitreous gel during aging is associated with a high risk of subsequent development of nuclear cataract. Many studies proved that oxidation is the key reason of nuclear cataract. Reactive oxygen species (ROS) are formed in mitochondria as a by-product of normal metabolism and as a consequence of exposure to environmental compounds. Therefore, mitochondrial DNA (mtDNA) is at particularly high risk of ROS-induced damage. Oxidative damage to mtDNA has been implicated as a causative factor in a wide variety of degenerative diseases and aging. However, the effect of mtDNA damage to the lens has not been studied. The goals of the study were to identify if there was increased mtDNA damage in lens when the eye were exposed to hyperoxic or hypoxic conditions and also to evaluate the changes in gene expression of mtDNA base excision repair (mtBER) enzymes. Our data have shown that the damage of mtDNA, the expression of mtBER enzymes and the level of 8-OHdG in lens increased after inspired hyperoxia, which is likely associated with oxidative stress. However, there was no effect to mtDNA and mtBER enzymes in lens after inspired hypoxia. Nuclear cataract appeared rapidly at 14 month old rats in hyperoxia group, and lens kept transparency in other groups.

  17. Fluorescence diagnosis of the status of the human lens in vivo

    NASA Astrophysics Data System (ADS)

    Vladimirova, E. S.; Salmin, V. V.; Salmina, A. B.; Oskirko, S. A.; Lazarenko, V. I.; Provorov, A. S.

    2012-03-01

    We have studied fluorescence spectra of the human lens in vivo for healthy eyes and in different stages of senile cataract development. We propose a spectral criterion, the lens opacity index, allowing us to differentiate between stages of cataract development. We show a high correlation between the stage of cataract development and the opacity index. We propose an empirical expression for determining the stage of senile cataract development from the value of the lens opacity index. The technique has been clinically tested.

  18. Ferulic Acid Suppresses Amyloid β Production in the Human Lens Epithelial Cell Stimulated with Hydrogen Peroxide

    PubMed Central

    Nagai, Noriaki; Kotani, Sachiyo; Mano, Yu; Ueno, Akina; Ito, Yoshimasa; Kitaba, Toshio; Takata, Takumi

    2017-01-01

    It is well known that oxidative stresses induce the production of amyloid β (Aβ) in the brain, lens, and retina, leading to age-related diseases. In the present study, we investigated the effects of ferulic acid on the Aβ levels in H2O2-stimulated human lens epithelial (HLE) SRA 01/04 cells. Three types of Aβ peptides (Aβ1-40, Aβ1-42, and Aβ1-43) were measured by ELISA, and the levels of mRNA for the expressed proteins related to Aβ production (APP, BACE1, and PS proteins) and degradation (ADAM10, NEP, and ECE1 proteins) were determined by quantitative real-time RT-PCR. H2O2 stimulation augmented gene expression of the proteins related to Aβ production, resulting in the production of three types of Aβ peptides. Treatment with 0.1 μM ferulic acid attenuated the augmentations of gene expression and production of the proteins related to the secretion of three types of Aβ peptides in the H2O2-stimulated HLE cells. These results provided evidence of antioxidative functions of ferulic acid for lens epithelial cells.

  19. Spatial analysis of human lens aquaporin-0 post-translational modifications by MALDI mass spectrometry tissue profiling.

    PubMed

    Gutierrez, Danielle B; Garland, Donita; Schey, Kevin L

    2011-12-01

    Aquaporin-0 (AQP0), the major integral membrane protein in lens fiber cells, becomes highly modified with increasing age. The functional consequences of these modifications are being revealed, and the next step is to determine how these modifications affect the ocular lens, which is directly related to their abundances and spatial distributions. The aim of this study was to utilize matrix-assisted laser desorption ionization (MALDI) direct tissue profiling methods, which produce spatially-resolved protein profiles, to map and quantify AQP0 post-translational modifications (PTMs). Direct tissue profiling was performed using frozen, equatorial human lens sections of various ages prepared by conditions optimized for MALDI mass spectrometry profiling of membrane proteins. Modified forms of AQP0 were identified and further investigated using liquid chromatography tandem mass spectrometry (LC-MS/MS). The distributions of unmodified, truncated, and oleoylated forms of AQP0 were examined with a maximum spatial resolution of 500 μm. Direct tissue profiling of intact human lens sections provided high quality, spatially-resolved, relative quantitative information of AQP0 and its modified forms indicating that 50% of AQP0 is truncated at a fiber cell age of 24 ± 1 year in all lenses examined. Furthermore, direct tissue profiling also revealed previously unidentified AQP0 modifications including N-terminal acetylation and carbamylation. N-terminal acetylation appears to provide a protective effect against N-terminal truncation.

  20. Alpha-A crystallin: quantitation of C-terminal modification during lens aging

    NASA Technical Reports Server (NTRS)

    Takemoto, L.; Gopalakrishnan, S.; Spooner, B. S. (Principal Investigator)

    1994-01-01

    Previous studies have demonstrated that the C-terminal region of alpha-A crystallin is susceptible to age-dependent, posttranslational modification. To quantitate the amount of modification, alpha-A crystallin was purified from total proteins of the aging bovine lens, then digested with lys-C endoproteinase. Reverse phase, high pressure liquid chromatography was used to resolve and quantitate the resulting peptides, to determine the amount of C-terminal peptide relative to peptides from other regions of the protein that have not been reported to undergo modification. The results indicate that relative to alpha-A crystallin from newborn lens, posttranslational modification has occurred in approximately 45-55% of the C-terminal region from mature lens. These results demonstrate extensive modification of the C-terminal region of alpha-A crystallin from the mature lens, indicating that during the aging process, posttranslational modifications in this region may make significant contributions to the aggregated state and/or molecular chaperone properties of the molecule.

  1. Shakespeare through the Lens of a New Age.

    ERIC Educational Resources Information Center

    Tabers-Kwak, Linda; Kaufman, Timothy U.

    2002-01-01

    Discusses two approaches that engage both students and teachers as they come to share an understanding of Shakespeare's relevance to all ages. Suggests teaching Shakespeare through picture books and through music. Notes that one of the first ways to modernize Shakespeare is to allow students to interact with the work. (SG)

  2. Proton Irradiation Alters Expression of FGF-2 In Human Lens Epithelial Cells

    NASA Technical Reports Server (NTRS)

    Blakely, E. A.; Bjornstad, K. A.; Chang, P. Y.; McNamara, M. P.; Chang, E.

    1999-01-01

    We are investigating a role for proton radiation-induced changes in FGF-2 gene expression as part of the mechanism(s) underlying lens cell injury. Radiation injury to the human lens is associated with the induction of cataract following exposure to protons.

  3. The Effect of Age on Compensation for a Negative Lens and Recovery from Lens-induced Myopia in Tree Shrews (Tupaia glis belangeri)

    PubMed Central

    Norton, Thomas T.; Amedo, Angela O.; Siegwart, John T.

    2010-01-01

    We examined in tree shrews the effect of age on the development of, and recovery from, myopia induced with a negative lens. Starting at 11, 16, 24, 35 or 48 days after natural eye-opening (days of visual experience [VE]), juvenile tree shrews (n = 5 per group) wore a monocular −5 D lens for 11 days. A long-term lens-wear group (n=6) began treatment at 16 days of VE and wore the lens for 30 days. A young adult group (n = 5) began to wear a −5 D lens between 93 and 107 days of VE (mean ± SD, 100 ± 6 days of VE) and wore the lens for 29 to 54 days (mean ± SD, 41.8 ± 9.8 days). The recovery phase in all groups was started by discontinuing −5 D lens wear. Contralateral control eyes in the three youngest groups were compared with a group of age-matched normal eyes and showed a small (<1 D), transient myopic shift. The amount of myopia that developed during lens wear was measured as the difference between the treated and control eye refractions. After 11 days of lens wear, the induced myopia was similar for the four younger groups (near full compensation: 11 day, −5.1 ± 0.4 D; 16 day, −4.7 ± 0.3 D, 24 day, −4.9 ± 0.4 D; 35 day, −4.0 ± 0.02) and slightly less in the oldest juvenile group (48 day, −3.3 ± 0.5 D). The young adult animals developed −4.8 ± 0.3 D of myopia after a longer lens-wear period. The rate of compensation (D/day) was high in the 4 youngest groups and decreased in the 48-day and young adult groups. The refractions of the long-term lens-wear juvenile group remained stable after compensating for the −5 D lens. During recovery, all animals in the youngest group recovered fully (< 1 D residual myopia) within seven days. Examples of both rapid (< 10 days) and slow recovery (> 12 days) occurred in all age groups except the youngest. Every animal showed more rapid recovery (higher recovery slope) in the first 4 days than afterward. One animal showed extremely slow recovery. Based on the time-course of myopia development observed in

  4. The effect of age on compensation for a negative lens and recovery from lens-induced myopia in tree shrews (Tupaia glis belangeri).

    PubMed

    Norton, Thomas T; Amedo, Angela O; Siegwart, John T

    2010-03-17

    We examined in tree shrews the effect of age on the development of, and recovery from, myopia induced with a negative lens. Starting at 11, 16, 24, 35 or 48days after natural eye-opening (days of visual experience [VE]), juvenile tree shrews (n=5 per group) wore a monocular -5D lens for 11days. A long-term lens-wear group (n=6) began treatment at 16days of VE and wore the lens for 30days. A young adult group (n=5) began to wear a -5D lens between 93 and 107days of VE (mean+/-SD, 100+/-6days of VE) and wore the lens for 29-54days (mean+/-SD, 41.8+/-9.8days). The recovery phase in all groups was started by discontinuing -5D lens wear. Contralateral control eyes in the three youngest groups were compared with a group of age-matched normal eyes and showed a small (<1D), transient myopic shift. The amount of myopia that developed during lens wear was measured as the difference between the treated and control eye refractions. After 11days of lens wear, the induced myopia was similar for the four younger groups (near full compensation: 11days, -5.1+/-0.4D; 16days, -4.7+/-0.3D; 24days, -4.9+/-0.4D; 35days, -4.0+/-0.02) and slightly less in the oldest juvenile group (48days, -3.3+/-0.5D). The young adult animals developed -4.8+/-0.3D of myopia after a longer lens-wear period. The rate of compensation (D/day) was high in the 4 youngest groups and decreased in the 48-day and young adult groups. The refractions of the long-term lens-wear juvenile group remained stable after compensating for the -5D lens. During recovery, all animals in the youngest group recovered fully (<1D residual myopia) within 7days. Examples of both rapid (<10days) and slow recovery (>12days) occurred in all age groups except the youngest. Every animal showed more rapid recovery (higher recovery slope) in the first 4days than afterward. One animal showed extremely slow recovery. Based on the time-course of myopia development observed in the youngest age groups, the start of the susceptible period for

  5. [Estimation of age-related features of acoustic density and biometric relations of lens based on combined ultrasound scanning].

    PubMed

    Avetisov, K S; Markosian, A G

    2013-01-01

    Results of combined ultrasound scanning for estimation of acoustic lens density and biometric relations of lens and other eye structures are presented. A group of 124 patients (189 eyes) was studied; they were subdivided depending on age and length of anteroposterior axis of the eye. Examination algorithm was developed that allows selective estimation of acoustic density of different lens zones and biometric measurements including volumetric. Age-related increase of acoustic density of different lens zones was revealed that indirectly shows method efficiency. Biometric studies showed almost concurring volumetric lens measurements in "normal" and "short" eyes in spite of significantly thicker central zone of the latter. Significantly lower correlation between anterior chamber volume and width of its angle was revealed in "short" eyes and "normal" and "long" eyes (correlation coefficients 0.37, 0.68 and 0.63 respectively).

  6. The Significance of the Discordant Occurrence of Lens Tumors in Humans versus Other Species

    PubMed Central

    Albert, Daniel M.; Phelps, Paul O.; Surapaneni, Krishna R.; Thuro, Bradley A.; Potter, Heather D.; Ikeda, Akihiro; Teixeira, Leandro B. C.; Dubielzig, Richard R.

    2015-01-01

    Purpose The purpose of this study was to determine in which species and under what conditions lens tumors occur. Design A review of data bases of available human and veterinary ocular pathological material and the previously reported literature. Participants Approximately 18,000 patients who had ocular surgical specimens submitted and studied at the University of Wisconsin School of Medicine and Public Health (UWSMPH) between 1920 and 2014 and 45,000 ocular veterinary cases from the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) between 1983 and 2014. Methods Material in two major archived collections at the University of Wisconsin medical and veterinary schools were studied for occurrence of lens tumors. Tumor was defined as “a new growth of tissue characterized by progressive, uncontrolled proliferation of cells.” In addition, cases presented at 3 major eye pathology societies (Verhoeff-Zimmerman Ophthalmic Pathology Society, Eastern Ophthalmic Pathology Society, and The Armed Forces Institute of Pathology Ophthalmic Alumni Society) from 1975 through 2014 were reviewed. Finally, a careful search of the literature was carried out. Approval from the IRB to carry out this study was obtained. Main Outcome Measures The presence of tumors of the lens. Results The database search and literature review failed to find an example of a lens tumor in humans. In contrast, examples of naturally occurring lens tumors were found in cats, dogs, rabbits, and birds. 4.5% of feline intraocular and adnexal neoplasms (234/5153) in the veterinary school database were designated as feline ocular post-traumatic sarcoma (FOPTS), a tumor previously demonstrated to be of lens epithelial origin. Similar tumors were seen in rabbit eyes, a bird, and in a dog. All four species with lens tumors had a history of either ocular trauma or protracted uveitis. The literature search also revealed cases where lens tumors were induced in zebrafish, rainbow trout, hamsters, and mice, by

  7. Dose conversion coefficients for neutron exposure to the lens of the human eye

    SciTech Connect

    Manger, Ryan P; Bellamy, Michael B; Eckerman, Keith F

    2011-01-01

    Dose conversion coefficients for the lens of the human eye have been calculated for neutron exposure at energies from 1 x 10{sup -9} to 20 MeV and several standard orientations: anterior-to-posterior, rotational and right lateral. MCNPX version 2.6.0, a Monte Carlo-based particle transport package, was used to determine the energy deposited in the lens of the eye. The human eyeball model was updated by partitioning the lens into sensitive and insensitive volumes as the anterior portion (sensitive volume) of the lens being more radiosensitive and prone to cataract formation. The updated eye model was used with the adult UF-ORNL mathematical phantom in the MCNPX transport calculations.

  8. Retinal images in the human eye with implanted intraocular lens

    NASA Astrophysics Data System (ADS)

    Zając, Marek; Siedlecki, Damian; Nowak, Jerzy

    2007-04-01

    A typical proceeding in cataract is based on the removal of opaque crystalline lens and inserting in its place the artificial intraocular lens (IOL). The quality of retinal image after such procedure depends, among others, on the parameters of the IOL, so the design of the implanted lens is of great importance. An appropriate choice of the IOL material, especially in relation to its biocompatibility, is often considered. However the parameter, which is often omitted during the IOL design is its chromatic aberration. In particular lack of its adequacy to the chromatic aberration of a crystalline lens may cause problems. In order to fit better chromatic aberration of the eye with implanted IOL to that of the healthy eye we propose a hybrid - refractive-diffractive IOL. It can be designed in such way that the total longitudinal chromatic aberration of an eye with implanted IOL equals the total longitudinal chromatic aberration of a healthy eye. In this study we compare the retinal image quality calculated numerically on the basis of the well known Liou-Brennan eye model with typical IOL implanted with that obtained if the IOL is done as hybrid (refractive-diffractive) design.

  9. Lens epithelial cell apoptosis appears to be a common cellular basis for non-congenital cataract development in humans and animals

    PubMed Central

    1995-01-01

    Cataract is a major ocular disease that causes blindness in many developing countries of the world. It is well established that various factors such as oxidative stress, UV, and other toxic agents can induce both in vivo and in vitro cataract formation. However, a common cellular basis for this induction has not been previously recognized. The present study of lens epithelial cell viability suggests such a general mechanism. When lens epithelial cells from a group of 20 cataract patients 12 to 94 years old were analyzed by terminal deoxynucleotidyl transferase (TdT) labeling and DNA fragmentation assays, it was found that all of these patients had apoptotic epithelial cells ranging from 4.4 to 41.8%. By contrast, in eight normal human lenses of comparable age, very few apoptotic epithelial cells were observed. We suggest that cataract patients may have deficient defense systems against factors such as oxidative stress and UV at the onset of the disease. Such stress can trigger lens epithelial cell apoptosis that then may initiate cataract development. To test this hypothesis, it is also demonstrated here that hydrogen peroxide at concentrations previously found in some cataract patients induces both lens epithelial cell apoptosis and cortical opacity. Moreover, the temporal and spatial distribution of induced apoptotic lens epithelial cells precedes development of lens opacification. These results suggest that lens epithelial cell apoptosis may be a common cellular basis for initiation of noncongenital cataract formation. PMID:7790371

  10. Melatonin and Sleep-Wake Rhythms before and after Ocular Lens Replacement in Elderly Humans

    PubMed Central

    Giménez, Marina; Beersma, Domien; Daan, Serge; van der Pol, Bert; Kanis, Martijn; van Norren, Dick; Gordijn, Marijke

    2016-01-01

    Light of short wavelengths has been shown to play a key role in non-image forming responses. Due to aging, the ocular lens becomes more yellow reducing the transmission of short wavelengths in the elderly. In the present study, we make use of cataract surgery to investigate the effects of a relative increase of short wavelength transmission on melatonin- and sleep-wake rhythms (N = 14). We observed, on average, a delay of the sleep-wake and the nocturnal melatonin rhythms after cataract surgery. This delay is tentatively attributed to a relatively large increase of light transmittance in the evening hours more than an increase of the already relatively high light intensities found in the daytime. The later phase that we observed after cataract surgery (clear lens) as compared to the earlier phase observed before cataract (yellowish lens) is in agreement with the general later phase reported in the young (clear lens) population. PMID:26891336

  11. Thioredoxin Binding Protein-2 Regulates Autophagy of Human Lens Epithelial Cells under Oxidative Stress via Inhibition of Akt Phosphorylation

    PubMed Central

    Yao, Ke; Zhang, Yidong; Chen, Guangdi; Lai, Kairan; Yin, Houfa

    2016-01-01

    Oxidative stress plays an essential role in the development of age-related cataract. Thioredoxin binding protein-2 (TBP-2) is a negative regulator of thioredoxin (Trx), which deteriorates cellular antioxidant system. Our study focused on the autophagy-regulating effect of TBP-2 under oxidative stress in human lens epithelial cells (LECs). Human lens epithelial cells were used for cell culture and treatment. Lentiviral-based transfection system was used for overexpression of TBP-2. Cytotoxicity assay, western blot analysis, GFP/mCherry-fused LC3 plasmid, immunofluorescence, and transmission electronic microscopy were performed. The results showed that autophagic response of LECs with increased LC3-II, p62, and GFP/mCherry-LC3 puncta (P < 0.01) was induced by oxidative stress. Overexpression of TBP-2 further strengthens this response and worsens the cell viability (P < 0.01). Knockdown of TBP-2 attenuates the autophagic response and cell viability loss induced by oxidative stress. TBP-2 mainly regulates autophagy in the initiation stage, which is mTOR-independent and probably caused by the dephosphorylation of Akt under oxidative stress. These findings suggest a novel role of TBP-2 in human LECs under oxidative stress. Oxidative stress can cause cell injury and autophagy in LECs, and TBP-2 regulates this response. Hence, this study provides evidence regarding the role of TBP-2 in lens and the possible mechanism of cataract development. PMID:27656263

  12. Isolation and characterization of the 5'-flanking sequence of the human ocular lens MIP gene.

    PubMed

    Wang, X Y; Ohtaka-Maruyama, C; Pisano, M M; Jaworski, C J; Chepelinsky, A B

    1995-12-29

    The MIP (major intrinsic protein) gene, a member of an ancient family of membrane channel genes, encodes the predominant fiber cell membrane protein of the ocular lens. Its specific expression in the lens fibers is temporally and spatially regulated during development. To study the regulation of expression of MIP and delineate the regulatory elements underlying its tissue specificity and ontogenic profile, we have cloned 2840 bp of the human MIP 5'-flanking sequence. The human MIP 5'-flanking sequence contains three complete Alu repetitive elements in tandem at position between nt -1699 and -2684 (nt -1699/-2684). These Alu elements appear to have had a complex evolutionary history with insertions at different times. We have fused DNA fragments containing MIP 5'-flanking sequences to the bacterial cat reporter gene encoding chloramphenicol acetyltransferase and assayed them in primary cultures of chicken lens cells. We have mapped two negative regulatory regions in the human MIP 5'-flanking sequences -1564/-1696 and -948/-1000. We demonstrated that the human MIP 5'-flanking sequence -253/+42 contains a functional promoter in lens cells but is inactive in kidney epithelial cells or mouse fibroblasts, suggesting that this sequence contains regulatory elements responsible for the lens-specific expression of MIP.

  13. PARP-1 inhibition influences the oxidative stress response of the human lens

    PubMed Central

    Smith, Andrew J.O.; Ball, Simon S.R.; Bowater, Richard P.; Wormstone, I. Michael

    2016-01-01

    Poly(ADP-ribose) polymerase-1 (PARP-1) is best characterised for its involvement in DNA repair. PARP-1 activity is also linked to cell fate, confounding its roles in maintaining genome integrity. The current study assessed the functional roles of PARP-1 within human lens cells in response to oxidative stress. The human lens epithelial cell line FHL124 and whole human lens cultures were used as experimental systems. Hydrogen peroxide (H2O2) was employed to induce oxidative stress and cell death was assessed by LDH release. The functional influence of PARP-1 was assessed using targeted siRNA and chemical inhibition (by AG14361). Immunocytochemistry and western blotting were used to assess PARP-1 expression and the alkaline comet assay determined the levels of DNA strand breaks. PARP-1 was generally observed in the cell nucleus in both the FHL124 cell line and whole human lenses. PARP-1 inhibition rendered FHL124 cells more susceptible to H2O2-induced DNA strand breaks. Interestingly, reduction of PARP-1 activity significantly inhibited H2O2-induced cell death relative to control cells. Inhibition of PARP-1 in whole human lenses resulted in a reduced level of lens opacity and cell death following exposure to H2O2 relative to matched pair controls. Thus, we show that PARP-1 could play a role in the fate of human lens cells, and these first observations in human lenses suggest that it could impact on lens opacity. Further studies are required to elucidate the regulatory processes that give rise to these effects. PMID:26990173

  14. Predicting cattle age from eye lens weight and nitrogen content, dentition, and United States Department of Agriculture maturity score.

    PubMed

    Raines, C R; Dikeman, M E; Unruh, J A; Hunt, M C; Knock, R C

    2008-12-01

    This research explores the relationship between generally accepted and alternative cattle age-prediction methods and chronological age. Cattle (n = 386) of documented ages ranging from 370 to 1,115 d of age were used. Dentition (DEN), USDA maturity score (MS), lens weight (LW), and lens total N (LN) content were used as possible predictors of age. Correlations with age were determined: LW (r = 0.77); DEN (r = 0.74); LN (r = 0.71); and MS (r = 0.64). Stepwise backward regression was used to generate an age prediction equation: Age (mo) = -21.79 + 17.23(LW, g) + 0.038(DEN). By this equation, 38% of cattle age were verified as age. Independent measures verified the following percentages of cattle as age: LW (20.2%), MS (11.0%), DEN (9.6%), and LN (8.7%). The DEN verified that 87.6% were verified as <30 mo old, and LW verified 81.6% of cattle as <30 mo old. A separate group of cattle (n = 18) ranging in age from 1 to 12 yr were evaluated for lens properties, for which LW (R(2) = 0.91) and LN (R(2) = 0.92) were highly correlated with age. The LW and DEN were the best predictors of age for cattle 13- to 37-mo-old and yielded the most accurate age prediction when used in combination (R(2) = 0.67).

  15. The ability of lens alpha crystallin to protect against heat-induced aggregation is age-dependent

    NASA Technical Reports Server (NTRS)

    Horwitz, J.; Emmons, T.; Takemoto, L.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    Alpha crystallin was prepared from newborn and aged bovine lenses. SDS-PAGE and tryptic peptide mapping demonstrated that both preparations contained only the alpha-A and alpha-B chains, with no significant contamination of other crystallins. Compared with alpha crystallin from the aged lens, alpha crystallin from the newborn lens was much more effective in the inhibition of beta L crystallin denaturation and precipitation induced in vitro by heat. Together, these results demonstrate that during the aging process, the alpha crystallins lose their ability to protect against protein denaturation, consistent with the hypothesis that the alpha crystallins play an important role in the maintenance of protein native structure in the intact lens.

  16. The Effect of Lens-Induced Anisometropia on Accommodation and Vergence during Human Visual Development

    PubMed Central

    Candy, T. Rowan

    2011-01-01

    Purpose. Clear and single binocular vision, a prerequisite for normal human visual development, is achieved through accommodation and vergence. Anisometropia is associated with abnormal visual development, but its impact on accommodation and vergence, and therefore on the individual's visual experience, is not known. This study determined the impact of transiently induced anisometropia on accommodative and vergence performance of the typically developing human visual system. Methods. One hundred eighteen subjects (age range, 2.9 months to 41.1 years) watched a cartoon movie that moved between 80 and 33 cm under six different viewing conditions: binocular and monocular, and with ±2 diopters (D) and ±4 D of lens-induced anisometropia. Twenty-one subjects (age range, 3.1 months to 12.1 years) also watched the movie with 11% induced aniseikonia. Accommodation and vergence were recorded in both eyes using a videoretinoscope (25 Hz). Results. The main effect of viewing condition was statistically significant for both accommodation and vergence (both P < 0.001), with monocular accommodative and vergence gains statistically significantly smaller than the binocular and four induced anisometropia conditions (P < 0.001 for both accommodation and vergence). The main effect of age approached significance for accommodation (P = 0.06) and was not significant for vergence (P = 0.32). Accommodative and vergence gains with induced aniseikonia were not statistically significantly different from the binocular condition (both P > 0.5). Conclusions. Accommodative and vergence gains of the typically developing visual system deteriorated marginally (accommodation more than vergence) with transiently induced anisometropia (up to ±4 D) and did not deteriorate significantly with induced aniseikonia of 11%. Some binocular cues remained with ±4 D of induced anisometropia and 11% induced aniseikonia, as indicated by the accommodative and vergence gains being higher than in monocular viewing

  17. A 2D correlation Raman spectroscopy analysis of a human cataractous lens

    NASA Astrophysics Data System (ADS)

    Sacharz, Julia; Wesełucha-Birczyńska, Aleksandra; Paluszkiewicz, Czesława; Chaniecki, Piotr; Błażewicz, Marta

    2016-11-01

    This work is a continuation of our study of a cataractous human eye lens removed after phacoemulsification surgery. There are clear differences in the lens colors that allowed for distinguishing two opaque phases in the obtained biological material: the white- and yellow-phase. The Raman spectroscopy and 2D correlation spectroscopy method were used to trace a pathologically altered human cataract lens at a molecular level. Although the Raman spectra of these two phases are relatively similar, taking advantage of 2D correlation, and considering time as an external perturbation, the synchronous and asynchronous spectra were obtained showing completely different patterns. Prominent synchronous auto-peaks appear at 3340, 2920, 1736, 1665 and 1083 cm-1 for the white-, and at 2929 and 1670 cm-1 for the yellow phase. The white phase is characterized by intensive asynchronous peaks at -(2936, 3360), -(1650, 1674) and +(1620,1678). The modifications in the water contained in the white phase structure are ahead of the changes in the protein (CH3-groups), furthermore changes in β-conformation are asynchronous with respect to the α-structure. The yellow phase demonstrates asynchronous peaks: +(2857, 2928), +(1645,1673), +(1663, 1679), and +(1672,1707). These illustrate concomitant modifications in the β- and unordered conformation. Both forms of cataractous human eye lens, white- and yellow-phases, are degenerate forms of the eye lens proteins, both are arranged in a different way. The main differences are observed for the amide I, methyl, methylene and Osbnd H vibrational band region. The effect of Asp, Glu and Tyr amino acids in cataractous lens transformations was observed.

  18. A Simple Model of the Accommodating Lens of the Human Eye

    ERIC Educational Resources Information Center

    Oommen, Vinay; Kanthakumar, Praghalathan

    2014-01-01

    The human eye is often discussed as optically equivalent to a photographic camera. The iris is compared with the shutter, the pupil to the aperture, and the retina to the film, and both have lens systems to focus rays of light. Although many similarities exist, a major difference between the two systems is the mechanism involved in focusing an…

  19. Are Older Adults Less Embodied? A Review of Age Effects through the Lens of Embodied Cognition

    PubMed Central

    Costello, Matthew C.; Bloesch, Emily K.

    2017-01-01

    Embodied cognition is a theoretical framework which posits that cognitive function is intimately intertwined with the body and physical actions. Although the field of psychology is increasingly accepting embodied cognition as a viable theory, it has rarely been employed in the gerontological literature. However, embodied cognition would appear to have explanatory power for aging research given that older adults typically manifest concurrent physical and mental changes, and that research has indicated a correlative relationship between such changes. The current paper reviews age-related changes in sensory processing, mental representation, and the action-perception relationship, exploring how each can be understood through the lens of embodied cognition. Compared to younger adults, older adults exhibit across all three domains an increased tendency to favor visual processing over bodily factors, leading to the conclusion that older adults are less embodied than young adults. We explore the significance of this finding in light of existing theoretical models of aging and argue that embodied cognition can benefit gerontological research by identifying further factors that can explain the cause of age-related declines. PMID:28289397

  20. Acanthamoeba keratitis in a non-contact lens wearer with human immunodeficiency virus.

    PubMed

    Hansen, Birgitte; Kronborg, Gitte

    2003-01-01

    Acanthamoeba keratitis is potentially blinding and often associated with contact lens wearing. A human immunodeficiency virus (HIV)-positive patient, a non-contact lens wearer, presented with keratitis. She experienced a protracted course of disease, characterized by exacerbations and remissions, and was treated with various topical antibiotics and steroids. 13 months after symptom onset the eye was removed owing to serious scarring of cornea and unbearable pain. Microbiological and histopathological examination of the cornea showed Acanthamoeba. In non-contact lens wearers suffering from Acanthamoeba keratitis the diagnosis is delayed, pathognomonic features are often not seen and visual outcome is usually poor. There is no known relation between HIV infection and Acanthamoeba keratitis.

  1. The effect of lens aging and cataract surgery on circadian rhythm

    PubMed Central

    Yan, Shen-Shen; Wang, Wei

    2016-01-01

    Many organisms have evolved an approximately 24-hour circadian rhythm that allows them to achieve internal physiological homeostasis with external environment. Suprachiasmatic nucleus (SCN) is the central pacemaker of circadian rhythm, and its activity is entrained to the external light-dark cycle. The SCN controls circadian rhythm through regulating the synthesis of melatonin by pineal gland via a multisynaptic pathway. Light, especially short-wavelength blue light, is the most potent environmental time cue in circadian photoentrainment. Recently, the discovery of a novel type of retinal photoreceptors, intrinsically photosensitive retinal ganglion cells, sheds light on the mechanism of circadian photoentrainment and raises concerns about the effect of ocular diseases on circadian system. With age, light transmittance is significantly decreased due to the aging of crystalline lens, thus possibly resulting in progressive loss of circadian photoreception. In the current review, we summarize the circadian physiology, highlight the important role of light in circadian rhythm regulation, discuss about the correlation between age-related cataract and sleep disorders, and compare the effect of blue light- filtering intraocular lenses (IOLs) and ultraviolet only filtering IOLs on circadian rhythm. PMID:27500118

  2. The effect of lens aging and cataract surgery on circadian rhythm.

    PubMed

    Yan, Shen-Shen; Wang, Wei

    2016-01-01

    Many organisms have evolved an approximately 24-hour circadian rhythm that allows them to achieve internal physiological homeostasis with external environment. Suprachiasmatic nucleus (SCN) is the central pacemaker of circadian rhythm, and its activity is entrained to the external light-dark cycle. The SCN controls circadian rhythm through regulating the synthesis of melatonin by pineal gland via a multisynaptic pathway. Light, especially short-wavelength blue light, is the most potent environmental time cue in circadian photoentrainment. Recently, the discovery of a novel type of retinal photoreceptors, intrinsically photosensitive retinal ganglion cells, sheds light on the mechanism of circadian photoentrainment and raises concerns about the effect of ocular diseases on circadian system. With age, light transmittance is significantly decreased due to the aging of crystalline lens, thus possibly resulting in progressive loss of circadian photoreception. In the current review, we summarize the circadian physiology, highlight the important role of light in circadian rhythm regulation, discuss about the correlation between age-related cataract and sleep disorders, and compare the effect of blue light- filtering intraocular lenses (IOLs) and ultraviolet only filtering IOLs on circadian rhythm.

  3. Dose conversion coefficients for photon exposure of the human eye lens

    NASA Astrophysics Data System (ADS)

    Behrens, R.; Dietze, G.

    2011-01-01

    In recent years, several papers dealing with the eye lens dose have been published, because epidemiological studies implied that the induction of cataracts occurs even at eye lens doses of less than 500 mGy. Different questions were addressed: Which personal dose equivalent quantity is appropriate for monitoring the dose to the eye lens? Is a new definition of the dose quantity Hp(3) based on a cylinder phantom to represent the human head necessary? Are current conversion coefficients from fluence to equivalent dose to the lens sufficiently accurate? To investigate the latter question, a realistic model of the eye including the inner structure of the lens was developed. Using this eye model, conversion coefficients for electrons have already been presented. In this paper, the same eye model—with the addition of the whole body—was used to calculate conversion coefficients from fluence (and air kerma) to equivalent dose to the lens for photon radiation from 5 keV to 10 MeV. Compared to the values adopted in 1996 by the International Commission on Radiological Protection (ICRP), the new values are similar between 40 keV and 1 MeV and lower by up to a factor of 5 and 7 for photon energies at about 10 keV and 10 MeV, respectively. Above 1 MeV, the new values (calculated without kerma approximation) should be applied in pure photon radiation fields, while the values adopted by the ICRP in 1996 (calculated with kerma approximation) should be applied in case a significant contribution from secondary electrons originating outside the body is present.

  4. Acetylation of αA-crystallin in the human lens: Effects on structure and chaperone function

    PubMed Central

    Nagaraj, Ram H.; Nahomi, Rooban B.; Shanthakumar, Shilpa; Linetsky, Mikhail; Padmanabha, Smitha; Pasupuleti, Nagarekha; Wang, Benlian; Santhoshkumar, Puttur; Panda, Alok Kumar; Biswas, Ashis

    2011-01-01

    α-Crystallin is a major protein in the human lens that is perceived to help to maintain the transparency of the lens through its chaperone function. In this study, we demonstrate that many lens proteins including αA-crystallin are acetylated in vivo. We found that K70 and K99 in αA-crystallin and, K92 and K166 in αB-crystallin are acetylated in the human lens.To determine the effect of acetylation on the chaperone function and structural changes, αA-crystallin was acetylated using acetic anhydride. The resulting protein showed strong immunoreactivity against a Nε-acetyllysine antibody, which was directly related to the degree of acetylation. When compared to the unmodified protein, the chaperone function of the in vitro acetylated αA-crystallin was higher against three of the four different client proteins tested. Because a lysine (residue 70; K70) in αA-crystallin is acetylated in vivo, we generated a protein with an acetylation mimic, replacing Lys70 with glutamine (K70Q). The K70Q mutant protein showed increased chaperone function against three client proteins compared to the Wt protein but decreased chaperone function against γ-crystallin. The acetylated protein displayed higher surface hydrophobicity and tryptophan fluorescence, had altered secondary and tertiary structures and displayed decreased thermodynamic stability. Together, our data suggest that acetylation of αA-crystallin occurs in the human lens and that it could affect the chaperone function of αA-crystallin. PMID:22120592

  5. Occupational health nursing practice through the Human Caring lens.

    PubMed

    Noel, Dianne L

    2010-01-01

    Many health care and academic centers have adopted Watson's Theory of Human Caring as their guiding principle; the theory is also used in other disciplines, such as library science. Human caring theory offers occupational health nurses as structure that not only defines a focus for practice, but also provides a basis for moral and philosophical practice analyses. In particular, nurses may find this theory useful in confirming the definition of "caring" and reconsidering what nursing is all about. More importantly, consideration and application of this theory may lead to research on its applicability to the field of occupational health nursing. This article presents the science and philosophy of human caring, specifically Watson's Theory of Human Caring. Two case studies are presented that demonstrate how the theory could be used to evaluate occupational health nursing practice. To demonstrate its possible relevance as an occupational health nursing framework, an analysis of and comparison to existing occupational health nursing guidelines are detailed and discussed.

  6. Stretch-dependent changes in surface profiles of the human crystalline lens during accommodation: A finite element study

    PubMed Central

    Pour, Hooman Mohammad; Kanapathipillai, Sangarapillai; Zarrabi, Khosrow; Manns, Fabrice; Ho, Arthur

    2015-01-01

    Background A nonlinear isotropic finite element (FE) model of a 29 year old human crystalline lens was constructed to study the effects of various geometrical parameters on lens accommodation. Methods The model simulates dis-accommodation by stretching of the lens and predicts the change in the lens capsule, cortex and nucleus surface profiles at select states of stretching/accommodation. Multiple regression analysis (MRA) is used to develop a stretch-dependent mathematical model relating the lens sagittal height to the radial position of the lens surface as a function of dis-accommodative stretch. A load analysis is performed to compare the FE results to empirical results from lens stretcher studies. Using the predicted geometrical changes, the optical response of the whole eye during accommodation was analysed by ray-tracing. Results Aspects of lens shape change relative to stretch were evaluated including change in diameter (d), central thickness (T) and accommodation (A). Maximum accommodation achieved was 10.29 D. From the MRA, the stretch-dependent mathematical model of the lens shape related lens curvatures as a function of lens ciliary stretch well (maximum mean-square residual error 2.5×10−3 µm, p<0.001). The results are compared with those from in vitro studies. Conclusions The FE and ray-tracing predictions are consistent with EVAS studies in terms of load and power change versus change in thickness. The mathematical stretch-dependent model of accommodation presented may have utility in investigating lens behaviour at states other than the relaxed or fully-accommodated states. PMID:25727940

  7. Crystalline lens and refractive development.

    PubMed

    Iribarren, Rafael

    2015-07-01

    Individual refractive errors usually change along lifespan. Most children are hyperopic in early life. This hyperopia is usually lost during growth years, leading to emmetropia in adults, but myopia also develops in children during school years or during early adult life. Those subjects who remain emmetropic are prone to have hyperopic shifts in middle life. And even later, at older ages, myopic shifts are developed with nuclear cataract. The eye grows from 15 mm in premature newborns to approximately 24 mm in early adult years, but, in most cases, refractions are maintained stable in a clustered distribution. This growth in axial length would represent a refractive change of more than 40 diopters, which is compensated by changes in corneal and lens powers. The process which maintains the balance between the ocular components of refraction during growth is still under study. As the lens power cannot be measured in vivo, but can only be calculated based on the other ocular components, there have not been many studies of lens power in humans. Yet, recent studies have confirmed that the lens loses power during growth in children, and that hyperopic and myopic shifts in adulthood may be also produced by changes in the lens. These studies in children and adults give a picture of the changing power of the lens along lifespan. Other recent studies about the growth of the lens and the complexity of its internal structure give clues about how these changes in lens power are produced along life.

  8. Spectrum and Range of Oxidative Stress Responses of Human Lens Epithelial Cells to H2O2 Insult

    PubMed Central

    Goswami, Sumanta; Sheets, Nancy L.; Zavadil, Jiři; Chauhan, Bharesh K.; Bottinger, Erwin P.; Reddy, Venkat N.; Kantorow, Marc; Cvekl, Aleš

    2007-01-01

    Purpose Oxidative stress (OS) is believed to be a major contributor to age-related cataract and other age-related diseases. Methods cDNA microarrays were used to identify the spectrum and range of genes with transcript levels that are altered in response to acute H2O2-induced OS in human lens epithelial (HLE) cells. HLE cells were treated with 50 μM H2O2 for 1 hour in the absence of serum, followed by a return to complete medium. RNAs were prepared from treated and untreated cells at 0, 1, 2, and 8 hours after H2O2 treatment. Results The data showed 1171 genes that were significantly up- and downregulated in response to H2O2 treatment. Several functional subcategories of genes were identified, including those encoding DNA repair proteins, antioxidant defense enzymes, molecular chaperones, protein biosynthesis enzymes, and trafficking and degradation proteins. Differential expression of selected genes was confirmed at the level of RNA and/or protein. Many of the identified genes (e.g., glutathione S-transferase [MGST2], thioredoxin reductase β, and peroxiredoxin 2) have been identified as participants in OS responses in the lens and other systems. Some genes induced by OS in the current study (e.g., oxygen regulated protein [ORP150] and heat shock protein [HSP40]) are better known to respond to other forms of stress. Two genes (receptor tyrosine kinase [AXL/ARK] and protein phosphatase 2A) are known to be differentially expressed in cataract. Most of the genes point to a novel pathways associated with OS. Conclusions The present data provide a global perspective on those genes that respond to acute OS, point to novel genes and pathways associated with OS, and set the groundwork for understanding the functions of OS-related genes in lens protection and disease. PMID:12714647

  9. Molecular chaperone properties of the high molecular weight aggregate from aged lens

    NASA Technical Reports Server (NTRS)

    Takemoto, L.; Boyle, D.; Spooner, B. S. (Principal Investigator)

    1994-01-01

    The high molecular weight aggregate (HMWA) fraction was isolated from the water soluble proteins of aged bovine lenses. Its composition and ability to inhibit heat-induced denaturation and aggregation were compared with the lower molecular weight, oligomeric fraction of alpha isolated from the same lens. Although the major components of both fractions were the alpha-A and alpha-B chains, the HMWA fraction possessed a decreased ability to protect other proteins against heat-induced denaturation and aggregation. Immunoelectron microscopy of both fractions demonstrated that alpha particles from the HMWA fraction contained increased amounts of beta and gamma crystallins, bound to a central region of the supramolecular complex. Together, these results demonstrate that alpha crystallins found in the HMWA fraction possess a decreased ability to protect against heat-induced denaturation and aggregation, and suggest that at least part of this decrease could be due to the increased presence of beta and gamma crystallins complexed to the putative chaperone receptor site of the alpha particles.

  10. Hypericin-mediated photooxidative damage of α-crystallin in human lens epithelial cells.

    PubMed

    Ehrenshaft, Marilyn; Roberts, Joan E; Mason, Ronald P

    2013-07-01

    St. John's wort (Hypericum perforatum), a perennial herb native to Europe, is widely used for and seems to be effective in treatment of mild to moderate depression. Hypericin, a singlet oxygen-generating photosensitizer that absorbs in both the visible and the UVA range, is considered to be one of the bioactive ingredients of St. John's wort, and commercial preparations are frequently calibrated to contain a standard concentration. Hypericin can accumulate in ocular tissues, including lenses, and can bind in vitro to α-crystallin, a major lens protein. α-crystallin is required for lens transparency and also acts as a chaperone to ensure its own integrity and the integrity of all lens proteins. Because there is no crystallin turnover, damage to α-crystallin is cumulative over the lifetime of the lens and can lead to cataracts, the principal cause of blindness worldwide. In this work we study hypericin photosensitization of α-crystallin and detect extensive polymerization of bovine α-crystallin exposed in vitro to hypericin and UVA. We use fluorescence confocal microscopy to visualize binding between hypericin and α-crystallin in a human lens epithelial (HLE) cell line. Further, we show that UVA irradiation of hypericin-treated HLE cells results in a dramatic decrease in α-crystallin detection concurrent with a dramatic accumulation of the tryptophan oxidation product N-formylkynurenine (NFK). Examination of actin in HLE cells indicates that this cytoskeleton protein accumulates NFK resulting from hypericin-mediated photosensitization. This work also shows that filtration of wavelengths <400nm provides incomplete protection against α-crystallin modification and NFK accumulation, suggesting that even by wearing UV-blocking sunglasses, routine users of St. John's wort cannot adequately shield their lenses from hypericin-mediated photosensitized damage.

  11. Hypericin-Mediated Photooxidative Damage of α-crystallin in Human Lens Epithelial Cells

    PubMed Central

    Ehrenshaft, Marilyn; Roberts, Joan E.; Mason, Ronald P.

    2013-01-01

    St. John's wort (Hypericum perforatum), a perennial herb native to Europe, is widely used and appears to be effective in treatment of mild to moderate depression. Hypericin, a singlet oxygen-generating photosensitizer that absorbs in both the visible and UVA range, is considered to be one of the bioactive ingredients, and commercial preparations are frequently calibrated to contain a standard concentration. Hypericin can accumulate in ocular tissues, including lenses, and can bind in vitro to α-crystallin, a major lens protein. Alpha-crystallin is required for lens transparency and also acts as a chaperone to ensure its own integrity and the integrity of all lens proteins. Because there is no crystallin turnover, damage to α-crystallin is cumulative over the lifetime of the lens, and can lead to cataracts, the principal cause of blindness worldwide. In this work we study hypericin photosensitization of α-crystallin and detect extensive polymerization of bovine α-crystallin exposed in vitro to hypericin and UVA. We use fluorescent confocal microscopy to visualize binding between hypericin and α-crystallin in a human lens epithelial (HLE) cell line. Further, we show that UVA irradiation of hypericin-treated HLE cells results in a dramatic decrease in α-crystallin detection concurrent with a dramatic accumulation of the tryptophan oxidation product N-formylkynurenine (NFK). Examination of actin in HLE cells indicates that this cytoskeleton protein accumulates NFK resulting from hypericin-mediated photosensitization. This work also shows that filtration of wavelengths <400 nm provides incomplete protection against α-crystallin modifications and NFK accumulation, suggesting that even by wearing UV blocking sunglasses, routine users of St. John's wort cannot adequately shield their lenses from hypericin-mediated photosensitized damage. PMID:23453985

  12. Deamidation alters the structure and decreases the stability of human lens betaA3-crystallin.

    PubMed

    Takata, Takumi; Oxford, Julie T; Brandon, Theodore R; Lampi, Kirsten J

    2007-07-31

    According to the World Health Organization, cataracts account for half of the blindness in the world, with the majority occurring in developing countries. A cataract is a clouding of the lens of the eye due to light scattering of precipitated lens proteins or aberrant cellular debris. The major proteins in the lens are crystallins, and they are extensively deamidated during aging and cataracts. Deamidation has been detected at the domain and monomer interfaces of several crystallins during aging. The purpose of this study was to determine the effects of two potential deamidation sites at the predicted interface of the betaA3-crystallin dimer on its structure and stability. The glutamine residues at the reported in vivo deamidation sites of Q180 in the C-terminal domain and at the homologous site Q85 in the N-terminal domain were substituted with glutamic acid residues by site-directed mutagenesis. Far-UV and near-UV circular dichroism spectroscopy indicated that there were subtle differences in the secondary structure and more notable differences in the tertiary structure of the mutant proteins compared to that of the wild type betaA3-crystallin. The Q85E/Q180E mutant also was more susceptible to enzymatic digestion, suggesting increased solvent accessibility. These structural changes in the deamidated mutants led to decreased stability during unfolding in urea and increased precipitation during heat denaturation. When simulating deamidation at both residues, there was a further decrease in stability and loss of cooperativity. However, multiangle-light scattering and quasi-elastic light scattering experiments showed that dimer formation was not disrupted, nor did higher-order oligomers form. These results suggest that introducing charges at the predicted domain interface in the betaA3 homodimer may contribute to the insolubilization of lens crystallins or favor other, more stable, crystallin subunit interactions.

  13. Finite element implementation of a multiscale model of the human lens capsule.

    PubMed

    Burd, H J; Regueiro, R A

    2015-11-01

    An axisymmetric finite element implementation of a previously described structural constitutive model for the human lens capsule (Burd in Biomech Model Mechanobiol 8(3):217-231, 2009) is presented. This constitutive model is based on a hyperelastic approach in which the network of collagen IV within the capsule is represented by an irregular hexagonal planar network of hyperelastic bars, embedded in a hyperelastic matrix. The paper gives a detailed specification of the model and the periodic boundary conditions adopted for the network component. Momentum balance equations for the network are derived in variational form. These balance equations are used to develop a nonlinear solution scheme to enable the equilibrium configuration of the network to be computed. The constitutive model is implemented within a macroscopic finite element framework to give a multiscale model of the lens capsule. The possibility of capsule wrinkling is included in the formulation. To achieve this implementation, values of the first and second derivatives of the strain energy density with respect to the in-plane stretch ratios need to be computed at the local, constitutive model, level. Procedures to determine these strain energy derivatives at equilibrium configurations of the network are described. The multiscale model is calibrated against previously published experimental data on isolated inflation and uniaxial stretching of ex vivo human capsule samples. Two independent example lens capsule inflation analyses are presented.

  14. Particle irradiation induces FGF2 expression in normal human lens cells

    NASA Technical Reports Server (NTRS)

    Chang, P. Y.; Bjornstad K, A.; Chang, E.; McNamara, M.; Barcellos-Hoff, M. H.; Lin, S. P.; Aragon, G.; Polansky, J. R.; Lui, G. M.; Blakely, E. A.

    2000-01-01

    Particle Irradiation Induces FGF2 Expression in Normal Human Lens Cells. Particle radiations, including both proton and helium-ion beams, have been used to successfully treat choroidal melanoma, but with the complication of radiation-induced cataract. We have investigated a role for radiation-induced changes in the expression of basic fibroblast growth factor (FGF2) gene expression as part of the mechanism(s) underlying lens cell injury associated with cataract. Normal human lens epithelial (HLE) cells were cultured in vitro on extracellular matrix (ECM) originated from bovine corneal endothelial cells. This study reports evidence for rapid but transient induction of FGF2 transcripts, an increase of between 5- and 8-fold, within 0.5 h after exposure to particle radiation, followed by another wave of increased transcription at 2-3 h postirradiation. Immunofluorescence results confirm the enhanced levels of FGF2 protein rapidly after exposure to protons or helium ions, followed by another wave of increased activity unique to helium at 6 h postirradiation. This second wave of increased immunoreactivity was not observed in the proton-irradiated samples. Total FGF2 protein analysis after helium-ion exposures shows induced expression of three FGF2 isoforms, with an increase of up to 2-fold in the 18-kDa low-molecular-weight species. Studies of the effects of protons on individual FGF2 protein isoforms are in progress. Several mechanisms involving a role for FGF2 in radiation-induced cataract are discussed.

  15. Path-dependent human identification using a pyroelectric infrared sensor and fresnel lens arrays.

    PubMed

    Fang, Jian-Shuen; Hao, Qi; Brady, David J; Shankar, Mohan; Guenther, Bob D; Pitsianis, Nikos P; Hsu, Ken Y

    2006-01-23

    This paper presents a design and development of a low power consumption, and low cost, human identification system using a pyroelectric infrared (PIR) sensor whose visibility is modulated by a Fresnel lens array. The optimal element number of the lens array for the identification system was investigated and the experimental results suggest that the lens array with more elements can yield a better performance in terms of identification and false alarm rates. The other parameters of the system configuration such as the height of sensor location and sensor-to-object distance were also studied to improve spectral distinctions among sensory data of human objects. The identification process consists of two parts: training and testing. For the data training, we employed a principal components regression (PCR) method to cluster data with respect to different registered objects at different speed levels. The feature data of different objects walking along the same path in training yet at random speeds are then tested against the pre-trained clusters to decide whether the target is registered, and which member of the registered group it is.

  16. Properties of Membranes Derived from the Total Lipids Extracted from the Human Lens Cortex and Nucleus

    PubMed Central

    Mainali, Laxman; Raguz, Marija; O’Brien, William J.; Subczynski, Witold K.

    2013-01-01

    Human lens lipid membranes prepared using a rapid solvent exchange method from the total lipids extracted from the clear lens cortex and nucleus of 41- to 60-year-old donors were investigated using electron paramagnetic resonance spin-labeling. Profiles of the phospholipid alkyl-chain order, fluidity, oxygen transport parameter, and hydrophobicity were assessed across coexisting membrane domains. Membranes prepared from the lens cortex and nucleus were found to contain two distinct lipid environments, the bulk phospholipid-cholesterol domain and the cholesterol bilayer domain (CBD). The alkyl chains of phospholipids were strongly ordered at all depths, indicating that the amplitude of the wobbling motion of alkyl chains was small. However, profiles of the membrane fluidity, which explicitly contain time (expressed as the spin-lattice relaxation rate) and depend on the rotational motion of spin labels, show relatively high fluidity of alkyl chains close to the membrane center. Profiles of the oxygen transport parameter and hydrophobicity have a rectangular shape and also indicate a high fluidity and hydrophobicity of the membrane center. The amount of CBD was greater in nuclear membranes than in cortical membranes. The presence of the CBD in lens lipid membranes, which at 37°C showed a permeability coefficient for oxygen about 60% smaller than across a water layer of the same thickness, would be expected to raise the barrier for oxygen transport across the fiber cell membrane. Properties of human membranes are compared with those obtained for membranes made of lipids extracted from cortex and nucleus of porcine and bovine eye lenses. PMID:23438364

  17. [Lens platform].

    PubMed

    Łukaszewska-Smyk, Agnieszka; Kałuzny, Józef

    2010-01-01

    The lens platform defines lens structure and lens material. Evolution of lens comprises change in their shape, angulation of haptens and transition of three-piece lens into one-piece lens. The lens fall into two categories: rigid (PMMA) and soft (siliconic, acrylic, colameric). The main lens maaterials are polymers (hydrophilic and hydrophobic). The lens platform has an effect on biocompatibility, bioadhesion, stability of lens in capsule, degree of PCO evolution and sensitiveness to laser damages.

  18. Three-dimensional ray tracing in spherical and elliptical generalized Luneburg lenses for application in the human eye lens.

    PubMed

    Gómez-Correa, J E; Coello, V; Garza-Rivera, A; Puente, N P; Chávez-Cerda, S

    2016-03-10

    Ray tracing in spherical Luneburg lenses has always been represented in 2D. All propagation planes in a 3D spherical Luneburg lens generate the same ray tracing, due to its radial symmetry. A geometry without radial symmetry generates a different ray tracing. For this reason, a new ray tracing method in 3D through spherical and elliptical Luneburg lenses using 2D methods is proposed. The physics of the propagation is shown here, which allows us to make a ray tracing associated with a vortex beam. A 3D ray tracing in a composite modified Luneburg lens that represents the human eye lens is also presented.

  19. Advances in lens implant technology

    PubMed Central

    Kampik, Anselm; Dexl, Alois K.; Zimmermann, Nicole; Glasser, Adrian; Baumeister, Martin; Kohnen, Thomas

    2013-01-01

    Cataract surgery is one of the oldest and the most frequent outpatient clinic operations in medicine performed worldwide. The clouded human crystalline lens is replaced by an artificial intraocular lens implanted into the capsular bag. During the last six decades, cataract surgery has undergone rapid development from a traumatic, manual surgical procedure with implantation of a simple lens to a minimally invasive intervention increasingly assisted by high technology and a broad variety of implants customized for each patient’s individual requirements. This review discusses the major advances in this field and focuses on the main challenge remaining – the treatment of presbyopia. The demand for correction of presbyopia is increasing, reflecting the global growth of the ageing population. Pearls and pitfalls of currently applied methods to correct presbyopia and different approaches under investigation, both in lens implant technology and in surgical technology, are discussed. PMID:23413369

  20. Contribution of the crystalline lens gradient refractive index to the accommodation amplitude in non-human primates: In vitro studies

    PubMed Central

    Maceo, Bianca M.; Manns, Fabrice; Borja, David; Nankivil, Derek; Uhlhorn, Stephen; Arrieta, Esdras; Ho, Arthur; Augusteyn, Robert C.; Parel, Jean-Marie

    2012-01-01

    The purpose of this study was to determine the contribution of the gradient refractive index to the change in lens power in hamadryas baboon and cynomolgus monkey lenses during simulated accommodation in a lens stretcher. Thirty-six monkey lenses (1.4–14.1 years) and twenty-five baboon lenses (1.8–28.0 years) were stretched in discrete steps. At each stretching step, the lens back vertex power was measured and the lens cross-section was imaged with optical coherence tomography. The radii of curvature for the lens anterior and posterior surfaces were calculated for each step. The power of each lens surface was determined using refractive indices of 1.365 for the outer cortex and 1.336 for the aqueous. The gradient contribution was calculated by subtracting the power of the surfaces from the measured lens power. In all lenses, the contribution of the surfaces and gradient increased linearly with the amplitude of accommodation. The gradient contributes on average 65 ± 3% for monkeys and 66 ± 3% for baboons to the total power change during accommodation. When expressed in percent of the total power change, the relative contribution of the gradient remains constant with accommodation and age in both species. These findings are consistent with Gullstrand’s intracapsular theory of accommodation. PMID:22131444

  1. Lycium barbarum Polysaccharides Protect Human Lens Epithelial Cells against Oxidative Stress–Induced Apoptosis and Senescence

    PubMed Central

    Wen, Yuechun; Liu, Lian; Guo, Xiaoling; Hou, Guanghui; Wang, Guifang; Zhong, Jingxiang

    2014-01-01

    Objectives We aimed to investigate the protective effect of Lycium barbarum polysaccharides (LBPs) against oxidative stress–induced apoptosis and senescence in human lens epithelial cells. Methods To study apoptosis, SRA01/04 cells, a human lens epithelial cell lines, were exposed to 200 µM hydrogen peroxide (H2O2) for 24 h with or without pretreatment with LBPs. Cell viability was measured using a Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis, intracellular reactive oxygen species (ROS), and the loss of mitochondria membrane potential (Δψm) were detected by flow cytometric analyses. Expression levels of Bcl-2 and Bax proteins were measured by western blot analysis. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were quantized using commercial enzymatic kits according to the manufacturer's instructions. To study senescence, SRA01/04 cells were pre-incubated with LBPs and all cells were then exposed to 100 µM H2O2 for 96 h. Cellular senescence was assessed by morphologic examination and senescence-associated β-galactosidase (SA-β-gal) staining. Results LBPs significantly reduced H2O2-induced cell apoptosis, the generation of ROS, the loss of Δψm, and the levels of MDA. LBPs also inhibited H2O2-induced downregulated Bcl-2 and upregulated Bax proteins and increased the levels of SOD and GSH enzyme activity. Moreover, LBPs significantly attenuated H2O2-induced cellular senescence. Conclusions These findings suggested that LBPs protect human lens epithelial cells from H2O2-induced apoptosis by modulating the generation of ROS, loss of Δψm, Bcl-2 family, and antioxidant enzyme activity and attenuating cellular senescence. PMID:25333784

  2. Cytoskeletal Drugs Prevent Posterior Capsular Opacification in Human Lens Capsule in vitro

    PubMed Central

    Sureshkumar, Jeyalakshmi; Haripriya, Aravind; Muthukkaruppan, Veerappan; Kaufman, Paul L.; Tian, Baohe

    2012-01-01

    Background To determine whether the cytoskeletal drugs H-7 and Latrunculin B (LAT-B) inhibit posterior capsular opacification (PCO) in the cultured human lens capsular bag. Methods Following extracapsular cataract (lens) extraction in human donor eyes, the capsular bag was prepared and cultured by standard techniques. Forty-eight capsular bags were studied, in which 13 were treated with H-7 (50, 100 or 300μM), 12 with 1% BSS (vehicle of H-7), 11 with LAT-B (2, 5 or 10μM), and 12 with 0.25% DMSO (vehicle of LAT-B). Forty out of the 48 capsular bags were from paired eyes of 20 donors with 1 bag being treated with H-7/LAT-B and the other with BSS/DMSO for each pair, including 20 for the H-7-BSS protocol and 20 for the LAT-B-DMSO protocol. The medium with the cytoskeletal drug/vehicle was replaced every 3–4 days for 4 weeks. PCO was assessed daily using inverted phase-contrast microscopy and scored on a 4-point scale. Results In all cultures with BSS or DMSO, residual lens epithelial cells (LECs) on the anterior capsule migrated to and proliferated on the posterior capsule by 3–7 days and apparent LEC growth on the posterior capsule with severe capsular wrinkling (PCO Grade 3) was seen by 2-3weeks. When treated continuously with H-7 or LAT-B, the migration and proliferation of LECs and the capsular wrinkling were inhibited in a dose-dependent manner, with the inhibition being complete (PCO Grade 0) in the 300μM H-7 (n=8, p<0.001) or 10μM LAT-B culture (n=3, p=0.002). Conclusion H-7 and LAT-B dose-dependently inhibited PCO formation in the cultured human lens capsular bags, suggesting that cytoskeletal drugs might prevent PCO formation after surgery in the human eye. PMID:22138731

  3. BAX gene over-expression via nucleofection to induce apoptosis in human lens epithelial cells.

    PubMed

    Fang, Yanwen; Mo, Xiaofen; Luo, Yi; Lu, Yi

    2012-09-01

    Despite significant advances in cataract surgery techniques, posterior capsule opacification (PCO) remains a common complication. In PCO, remaining epithelial cells cloud the lens capsule and impair postoperative vision. This in vitro study was designed to investigate the potential of a gene-based approach, specifically over-expression of the proapoptotic BAX gene, to prevent PCO. Human lens epithelial cells (HLECs) were transfected by nucleofection with a plasmid encoding a fusion protein of green fluorescent protein and human BAX. The expression levels of BAX and its antiapoptotic counterpart BCL2 were determined by realtime reverse transcription polymerase chain reaction, Western blotting and immunofluorescence. BAX over-expression-induced cell death was analyzed by fluorescence-activated cell sorting using the Annexin V antibody. Fluorescence microscopy and transmission electron microscopy were used to assess changes in morphology and ultrastructure. Differential expression of the downstream apoptosis-related factor, caspase 3, was detected by Western blotting. Nucleofection efficiency was high (nearly 80%). BAX-transfected HLECs showed remarkably enhanced BAX gene expression and BAX:BCL2 ratio, but relatively little change in endogenous BCL2 expression. BAX over-expression also led to significant cytotoxicity, induction of apoptosis-related characteristics and activation of caspase 3. In conclusion, our results indicate that BAX gene over-expression can trigger cell death in HLECs via an apoptotic pathway. Thus, BAX may be a promising candidate for human gene therapy to treat PCO.

  4. Goat's eye integrated with a human cataractous lens: A training model for phacoemulsification

    PubMed Central

    Sengupta, Sabyasachi; Dhanapal, Praveen; Nath, Manas; Haripriya, Aravind; Venkatesh, Rengaraj

    2015-01-01

    A relatively simple and inexpensive technique to train surgeons in phacoemulsification using a goat's eye integrated with a human cataractous nucleus is described. The goat's eye is placed on a bed of cotton within the lumen of a cylindrical container. This is then mounted on a rectangular thermocol so that the limbus is presented at the surgical field. After making a clear corneal entry with a keratome, the trainer makes a 5–5.5 mm continuous curvilinear capsulorhexis in the anterior lens capsule, creates a crater of adequate depth in the cortex and inserts the human nucleus within this crater in the goat's capsular bag. The surgical wound is sutured, and the goat's eye is ready for training. Creating the capsulorhexis with precision and making the crater of adequate depth to snugly accommodate the human nucleus are the most important steps to prevent excessive wobbling of the nucleus while training. PMID:25971179

  5. Growth and differentiation of human lens epithelial cells in vitro on matrix

    NASA Technical Reports Server (NTRS)

    Blakely, E. A.; Bjornstad, K. A.; Chang, P. Y.; McNamara, M. P.; Chang, E.; Aragon, G.; Lin, S. P.; Lui, G.; Polansky, J. R.

    2000-01-01

    PURPOSE: To characterize the growth and maturation of nonimmortalized human lens epithelial (HLE) cells grown in vitro. METHODS: HLE cells, established from 18-week prenatal lenses, were maintained on bovine corneal endothelial (BCE) extracellular matrix (ECM) in medium supplemented with basic fibroblast growth factor (FGF-2). The identity, growth, and differentiation of the cultures were characterized by karyotyping, cell morphology, and growth kinetics studies, reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, and Western blot analysis. RESULTS: HLE cells had a male, human diploid (2N = 46) karyotype. The population-doubling time of exponentially growing cells was 24 hours. After 15 days in culture, cell morphology changed, and lentoid formation was evident. Reverse transcription-polymerase chain reaction (RT-PCR) indicated expression of alphaA- and betaB2-crystallin, fibroblast growth factor receptor 1 (FGFR1), and major intrinsic protein (MIP26) in exponential growth. Western analyses of protein extracts show positive expression of three immunologically distinct classes of crystallin proteins (alphaA-, alphaB-, and betaB2-crystallin) with time in culture. By Western blot analysis, expression of p57(KIP2), a known marker of terminally differentiated fiber cells, was detectable in exponential cultures, and levels increased after confluence. MIP26 and gamma-crystallin protein expression was detected in confluent cultures, by using immunofluorescence, but not in exponentially growing cells. CONCLUSIONS: HLE cells can be maintained for up to 4 months on ECM derived from BCE cells in medium containing FGF-2. With time in culture, the cells demonstrate morphologic characteristics of, and express protein markers for, lens fiber cell differentiation. This in vitro model will be useful for investigations of radiation-induced cataractogenesis and other studies of lens toxicity.

  6. Potential pre-cataractous markers induced by low-dose radiation effects in cultured human lens cells

    NASA Astrophysics Data System (ADS)

    Blakely, E.; McNamara, M.; Bjornstad, K.; Chang, P.

    The human lens is one of the most radiosensitive organs of the body. Cataract, the opacification of the lens, is a late-appearing response to radiation damage. Recent evidence indicates that exposure to relatively low doses of space radiation are associated with an increased incidence and early appearance of human cataracts (Cucinotta et al., Radiat. Res. 156:460-466, 2001). Basic research in this area is needed to integrate the early responses of various late-responding tissues into our understanding and estimation of radiation risk for space travel. In addition, these studies may contribute to the development of countermeasures for the early lenticular changes, in order to prevent the late sequelae. Radiation damage to the lens is not life threatening but, if severe, can affect vision unless surgically corrected with synthetic lens replacement. The lens, however, may be a sensitive detector of radiation effects for other cells of ectodermal origin in the body for which there are not currently clear endpoints of low-dose radiation effects. We have investigated the dose-dependent expression of several radiation-responsive endpoints using our in vitro model of differentiating human lens epithelial cells (Blakely et al., Investigative Ophthalmology &Visual Sciences, 41(12):3898-3907, 2000). We have investigated radiation effects on several gene families that include, or relate to, DNA damage, cytokines, cell-cycle regulators, cell adhesion molecules, cell cytoskeletal function and apoptotic cell death. In this paper we will summarize some of our dose-dependent data from several radiation types, and describe the model of molecular and cellular events that we believe may be associated with precataractous events in the human lens after radiation exposure. This work was supported by NASA Grant #T-965W.

  7. Effect of cigarette smoking on copper, lead, and cadmium accumulation in human lens

    PubMed Central

    Cekic, O.

    1998-01-01

    AIM—To identify cigarette smoking as a risk factor for development of cataract, to determine the importance of copper, lead, and cadmium in cataractogenesis, and to learn about any relation between those elements.
METHODS—Copper, lead, and cadmium concentrations were measured by atomic absorption spectrophotometry in 37 cataractous and nine normal human lenses.
RESULTS—All three element accumulations in lenses with cataract were statistically meaningful. Lenticular copper, lead, and cadmium were increased significantly with cigarette smoking. Cadmium had a positive correlation both with lead and copper in cataractous lenses.
CONCLUSION—The accumulation of copper, lead, and cadmium occurs in cataract. The probable source of cadmium in humans is cigarettes. Lenticular cadmium accumulation also increases copper and lead precipitation in the lens. Cigarette smoking might be cataractogenic.

 Keywords: cigarettes; cataract; copper; lead; cadmium PMID:9613387

  8. [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.

  9. A critical meta-analysis of lens model studies in human judgment and decision-making.

    PubMed

    Kaufmann, Esther; Reips, Ulf-Dietrich; Wittmann, Werner W

    2013-01-01

    increase in values of the lens model components, b) reduced heterogeneity between studies, and c) increases the success of bootstrapping. We argue that psychometric meta-analysis is useful for accurately evaluating human judgment and show the success of bootstrapping.

  10. A Critical Meta-Analysis of Lens Model Studies in Human Judgment and Decision-Making

    PubMed Central

    Kaufmann, Esther; Reips, Ulf-Dietrich; Wittmann, Werner W.

    2013-01-01

    increase in values of the lens model components, b) reduced heterogeneity between studies, and c) increases the success of bootstrapping. We argue that psychometric meta-analysis is useful for accurately evaluating human judgment and show the success of bootstrapping. PMID:24391781

  11. A comparison of cyst age and assay method of the efficacy of contact lens disinfectants against Acanthamoeba

    PubMed Central

    Kilvington, S.; Anger, C.

    2001-01-01

    AIMS—(i) To determine effect of Acanthamoeba cyst age, method of production, and (ii) to assay technique on the efficacy of multipurpose solutions (MPS) and hydrogen peroxide based contact lens disinfectants. (iii) To establish if MPS can remove mature cysts from contact lenses according to the ISO/DIS 14729 regimen test for microbe removal.
METHODS—Immature and mature cysts of A polyphaga were tested against the MPS Opti-Free express and the hydrogen peroxide based solutions Oxysept 1Step and Oxysept 1 using two assay methods. Simulated patient regimen testing was performed with the Opti-Free express and Complete using mature cysts inoculated on to group I or group IV lenses.
RESULTS—Immature cysts were sensitive to disinfection by all solutions. No killing was observed with mature cysts with Opti-Free express, while immature cysts yielded a 1-2 log reduction in viability. Oxysept 1Step gave a 1.1 (SD 0.3) log reduction in mature cysts after 6 hours. Oxysept 1 gave a 2.4 (0.3) log reduction in mature cysts after 4 hours and a 3.8 (0.5) log reduction after 6 hours. Patient regimen testing using Opti-Free express and Complete resulted in no recovery of viable mature cysts from the contact lenses or from the soaking solutions.
CONCLUSION—Cyst age but not method of production used in this study influences the efficacy of contact lens disinfectants against Acanthamoeba. MPS are effective in removing cysts from contact lens surfaces and may have a role in the prevention of acanthamoeba keratitis.

 PMID:11222342

  12. Ascorbate free radical reductases and diaphorases in soluble fractions of the human lens.

    PubMed

    Bando, M; Obazawa, H

    1995-12-01

    Major and minor ascorbate free radical (AFR) reductases, with diaphorase activity, and three other diaphorases were separated from the human lens soluble fraction by DEAE-cellulose ion-exchange column chromatography. They were characterized for adsorptivity to ion-exchange and 5'AMP-Sepharose 4B affinity columns, kinetic properties, and substrate specificity. The latter diaphorases were closely correlated with NADH-cytochrome beta 5 reductase. The major and minor AFR reductases were regarded as a major diaphorase group different from two ubiquitous diaphorases, i.e., NADH-cytochrome beta 5 reductase and DT-diaphorase. A major AFR reductase was partially purified approximately 50 fold over the lens soluble fraction by ion-exchange, affinity, and gel filtration (Sephacryl S-200 HR) column chromatography. From the partially purified enzyme, 2 bands, one sharp and one diffuse, were obtained by native polyacrylamide gel electrophoresis. Two proteins, of 20 and 24 kDa, were identified in the active enzyme bands by SDS-polyacrylamide gel electrophoresis. This suggests that the 20 and/or 24 kDa proteins may be components of the major AFR reductase.

  13. Spatial distributions of phosphorylated membrane proteins aquaporin 0 and MP20 across young and aged human lenses.

    PubMed

    Gutierrez, Danielle B; Garland, Donita L; Schwacke, John H; Hachey, David L; Schey, Kevin L

    2016-08-01

    In the human ocular lens it is now realized that post-translational modifications can alter protein function and/or localization in fiber cells that no longer synthesize proteins. The specific sites of post-translational modification to the abundant ocular lens membrane proteins AQP0 and MP20 have been previously identified and their functional effects are emerging. To further understand how changes in protein function and/or localization induced by these modifications alter lens homeostasis, it is necessary to determine the spatial distributions of these modifications across the lens. In this study, a quantitative LC-MS approach was used to determine the spatial distributions of phosphorylated AQP0 and MP20 peptides from manually dissected, concentric layers of fiber cells from young and aged human lenses. The absolute amounts of phosphorylation were determined for AQP0 Ser235 and Ser229 and for MP20 Ser170 in fiber cells from the lens periphery to the lens center. Phosphorylation of AQP0 Ser229 represented a minor portion of the total phosphorylated AQP0. Changes in spatial distributions of phosphorylated APQ0 Ser235 and MP20 Ser170 correlated with regions of physiological interest in aged lenses, specifically, where barriers to water transport and extracellular diffusion form.

  14. Kinetic characteristics of ZENECA ZD5522, a potent inhibitor of human and bovine lens aldose reductase.

    PubMed

    Cook, P N; Ward, W H; Petrash, J M; Mirrlees, D J; Sennitt, C M; Carey, F; Preston, J; Brittain, D R; Tuffin, D P; Howe, R

    1995-04-18

    Aldose reductase (aldehyde reductase 2) catalyses the conversion of glucose to sorbitol, and methylglyoxal to acetol. Treatment with aldose reductase inhibitors (ARIs) is a potential approach to decrease the development of diabetic complications. The sulphonylnitromethanes are a recently discovered class of aldose reductase inhibitors, first exemplified by ICI215918. We now describe enzyme kinetic characterization of a second sulphonylnitromethane, 3',5'-dimethyl-4'-nitromethylsulphonyl-2-(2-tolyl)acetanilide (ZD5522), which is at least 10-fold more potent against bovine lens aldose reductase in vitro and which also has a greater efficacy for reduction of rat nerve sorbitol levels in vivo (ED95 = 2.8 mg kg-1 for ZD5522 and 20 mg kg-1 for ICI 215918). ZD5522 follows pure noncompetitive kinetics against bovine lens aldose reductase when either glucose or methylglyoxal is varied (K(is) = K(ii) = 7.2 and 4.3 nM, respectively). This contrasts with ICI 215918 which is an uncompetitive inhibitor (K(ii) = 100 nM) of bovine lens aldose reductase when glucose is varied. Against human recombinant aldose reductase, ZD5522 displays mixed noncompetitive kinetics with respect to both substrates (K(is) = 41 nM, K(ii) = 8 nM with glucose and K(is) = 52 nM, K(ii) = 3.8 nM with methylglyoxal). This is the first report of the effects of a sulphonylnitromethane on either human aldose reductase or utilization of methylglyoxal. These results are discussed with reference to a Di Iso Ordered Bi Bi mechanism for aldose reductase, where the inhibitors compete with binding of both the aldehyde substrate and alcohol product. This model may explain why aldose reductase inhibitors follow noncompetitive or uncompetitive kinetics with respect to aldehyde substrates, and X-ray crystallography paradoxically locates an ARI within the substrate binding site. Aldehyde reductase (aldehyde reductase 1) is closely related to aldose reductase. Inhibition of bovine kidney aldehyde reductase by ZD5522

  15. Curcumin inhibits proliferation of human lens epithelial cells: a proteomic analysis*

    PubMed Central

    Hu, Yan-hong; Huang, Xiu-rong; Qi, Ming-xin; Hou, Bu-yuan

    2012-01-01

    Objective: The incidence of after-cataracts [also known as posterior capsular opacification (PCO)] is between 30% and 50% three years following cataract surgery. Suppressing the proliferation of lens epithelial cells (LECs) is a primary goal in preventing PCO. Here, we investigated the proteomic regulation of the inhibitory effects of curcumin (Cur) on the proliferation of human lens epithelial B3 (HLE-B3) cells. Methods: Recombinant human basic fibroblast growth factor (rhbFGF) was used to induce proliferation of HLE-B3 cells, which were incubated with 20 mg/L Cur in a CO2 incubator for 24 h. Results: We found that the absorbance (A) value of rhbFGF group was significantly higher than the A value of the control group. Furthermore, the A value of the Cur group was significantly lower compared to the rhbFGF group, with an inhibition of 53.7%. Five different protein spots were obtained from proliferative HLE-B3 cells induced by rhbFGF. Eight different protein spots were obtained in HLE-B3 cells incubated with Cur. There were the common variational protein spots at mass/charge (m/z) ratios of 8 093 and 13 767 between rhbFGF group and control group as well as between the Cur group and rhbFGF group. Conclusions: These results show that Cur effectively inhibited HLE-B3 cell proliferation induced by rhbFGF. The protein spots at m/z of 8 093 and 13 767 may be the targets of Cur-induced inhibition of HLE-B3 cell proliferation. Cur may be a reliable and effective drug for prevention and treatment of polymerase chain reaction (PCR). PMID:22556179

  16. 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)

  17. 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)

  18. Gradient parameter and axial and field rays in the gradient-index crystalline lens model

    NASA Astrophysics Data System (ADS)

    Pérez, M. V.; Bao, C.; Flores-Arias, M. T.; Rama, M. A.; Gómez-Reino, C.

    2003-09-01

    Gradient-index models of the human lens have received wide attention in optometry and vision sciences for considering how changes in the refractive index profile with age and accommodation may affect refractive power. This paper uses the continuous asymmetric bi-elliptical model to determine gradient parameter and axial and field rays of the human lens in order to study the paraxial propagation of light through the crystalline lens of the eye.

  19. Cataract surgery with intraocular lens implantation in children aged 5-15 in local anaesthesia: visual outcomes and complications.

    PubMed

    Giles, Kagmeni; Christelle, Domngang; Yannick, Bilong; Fricke, Otto Herrmann; Wiedemann, Peter

    2016-01-01

    The aim of this study was to report feasibility, the visual outcomes and complications of pediatric cataract surgery with primary intraocular lens implantation in children aged 5 to15 years in local anesthesia. This retrospective interventional case series included 62 eyes from 50 children who underwent pediatrc cataract surgery with primary intraocular lens implantation at the Mana eye Clinic Nkongsamba between 2006 and 2015 Main outcome measures were: best-corrected post operative visual acuity, and intraoperative and postoperative complications. Mean age at surgery was 10.18 ± 3.21 years. Mean follow up length was 15.75 ± 3.36 weeks. Etiology included: 10 congenital cataracs (16.12%). 35 developmental cataracts (56.45%) and 17 traumatic cataracts (27.41%). The mean preoperative BCVA was logMAR 1.19 ± 0.33. (range 0.6-2.3). After cycloplegia refraction 2 weeks after surgery, the mean postoperative BCVA was log MAR 0.58 ± 0.88 ( range 0.5-1.8). The mean implanted IOL power was 22.01 ±3.16 D. IOL was succefuly implanted in 54 eyes (87.07%). Eight eyes (9.67%) were left aphakic. Increase in BCVA of 4 logMAR lines and above was recorded in 27 patients (43.55%). Intraoperative complications included: 4 posterior capsule holes with vitrous lost, 3 lenses subluxation and 1 case of iris dialyse. Late postoperative complications included: posterior capsular opacity which occurred in 16 patients, 3 posterior synechia, 2 retinal detachment. Peribulbar anaesthesia can be considered as a viable option in selected patients presenting developmental cataract undergoing cataract surgery in developing countries. Effort should be made to improve the early identification of congenital cataract and its early surgical intervention and prompt optical rehabilitation to prevent amblyopia.

  20. Cataract surgery with intraocular lens implantation in children aged 5-15 in local anaesthesia: visual outcomes and complications

    PubMed Central

    Giles, Kagmeni; Christelle, Domngang; Yannick, Bilong; Fricke, Otto Herrmann; Wiedemann, Peter

    2016-01-01

    The aim of this study was to report feasibility, the visual outcomes and complications of pediatric cataract surgery with primary intraocular lens implantation in children aged 5 to15 years in local anesthesia. This retrospective interventional case series included 62 eyes from 50 children who underwent pediatrc cataract surgery with primary intraocular lens implantation at the Mana eye Clinic Nkongsamba between 2006 and 2015 Main outcome measures were: best-corrected post operative visual acuity, and intraoperative and postoperative complications. Mean age at surgery was 10.18 ± 3.21 years. Mean follow up length was 15.75 ± 3.36 weeks. Etiology included: 10 congenital cataracs (16.12%). 35 developmental cataracts (56.45%) and 17 traumatic cataracts (27.41%). The mean preoperative BCVA was logMAR 1.19 ± 0.33. (range 0.6-2.3). After cycloplegia refraction 2 weeks after surgery, the mean postoperative BCVA was log MAR 0.58 ± 0.88 ( range 0.5-1.8). The mean implanted IOL power was 22.01 ±3.16 D. IOL was succefuly implanted in 54 eyes (87.07%). Eight eyes (9.67%) were left aphakic. Increase in BCVA of 4 logMAR lines and above was recorded in 27 patients (43.55%). Intraoperative complications included: 4 posterior capsule holes with vitrous lost, 3 lenses subluxation and 1 case of iris dialyse. Late postoperative complications included: posterior capsular opacity which occurred in 16 patients, 3 posterior synechia, 2 retinal detachment. Peribulbar anaesthesia can be considered as a viable option in selected patients presenting developmental cataract undergoing cataract surgery in developing countries. Effort should be made to improve the early identification of congenital cataract and its early surgical intervention and prompt optical rehabilitation to prevent amblyopia. PMID:27795795

  1. Spatially Directed Proteomics of the Human Lens Outer Cortex Reveals an Intermediate Filament Switch Associated With the Remodeling Zone

    PubMed Central

    Wenke, Jamie L.; McDonald, W. Hayes; Schey, Kevin L.

    2016-01-01

    Purpose To quantify protein changes in the morphologically distinct remodeling zone (RZ) and adjacent regions of the human lens outer cortex using spatially directed quantitative proteomics. Methods Lightly fixed human lens sections were deparaffinized and membranes labeled with fluorescent wheat germ agglutinin (WGA-TRITC). Morphology directed laser capture microdissection (LCM) was used to isolate tissue from four distinct regions of human lens outer cortex: differentiating zone (DF), RZ, transition zone (TZ), and inner cortex (IC). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) of the plasma membrane fraction from three lenses (21-, 22-, and 27-year) revealed changes in major cytoskeletal proteins including vimentin, filensin, and phakinin. Peptides from proteins of interest were quantified using multiple reaction monitoring (MRM) mass spectrometry and isotopically-labeled internal peptide standards. Results Results revealed an intermediate filament switch from vimentin to beaded filament proteins filensin and phakinin that occurred at the RZ. Several other cytoskeletal proteins showed significant changes between regions, while most crystallins remained unchanged. Targeted proteomics provided accurate, absolute quantification of these proteins and confirmed vimentin, periplakin, and periaxin decrease from the DF to the IC, while filensin, phakinin, and brain acid soluble protein 1 (BASP1) increase significantly at the RZ. Conclusions Mass spectrometry-compatible fixation and morphology directed laser capture enabled proteomic analysis of narrow regions in the human lens outer cortex. Results reveal dramatic cytoskeletal protein changes associated with the RZ, suggesting that one role of these proteins is in membrane deformation and/or the establishment of ball and socket joints in the human RZ. PMID:27537260

  2. Effect of ultraviolet A exposure on transport of compatible organic osmolytes in human lens epithelial cells.

    PubMed

    Wu, D Y; Zhang, J S

    2015-05-18

    Compatible organic osmolytes, such as betaine, myoinositol, and taurine, are involved in antioxidant defense, protein stabilization, and stress responses. This osmolyte strategy requires the expression of specific osmolyte transporters such as betaine (BGT-1), myoinositol (SMIT), and taurine (TAUT). In contrast to the kidney, keratinocytes, and neural cells, few studies have examined osmolytes in human lens epithelial cells (HLECs). We examined the expression of mRNA specific for BGT-1, SMIT, and TAUT in HLECs. In comparison to normoosmotic (305 mOsM) controls, there was a 3-5-fold time-dependent reaction of BGT-1, SMIT, and TAUT mRNA levels in HLECs exposed to hyperosmotic stress (405 mOsM). Maximal responses were obtained for BGT-1, SMIT, and TAUT mRNA expression after 3, 24 and 9 h of hyperosmotic exposure, respectively. This expression was correlated with increased osmolyte uptake. In contrast, hypoosmotic (205 mOsM) stimulation led to a significant efflux of osmolytes. Exposure to ultraviolet A (340-400 nm) radiation significantly stimulated osmolyte uptake. Increased osmolyte uptake was associated with upregulation of mRNA steady-state levels for osmolyte transporters in irradiated cells. These results demonstrate that ultraviolet A radiation leads to the accumulation of compatible organic osmolytes in HLECs as hyperosmotic pressure, which can maintain cellular environmental homeostasis.

  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. Effect of contact lens material on cytotoxicity potential of multipurpose solutions using human corneal epithelial cells

    PubMed Central

    Tanti, N.C.; Crockett, B.; Mansour, L.; Jones, L.

    2011-01-01

    Purpose Multipurpose solutions (MPS) are used daily to clean and disinfect silicone hydrogel (SiHy) contact lenses. This in vitro study was undertaken to identify the potential for interaction between MPS, SiHy surface treatments, and lens materials, which may lead to changes in the response of human corneal epithelial cells (HCEC) to MPS-soaked lenses. Methods The MPS tested were renu fresh (formerly known as ReNu MultiPlus; ReNu), OptiFree Express (OFX), OptiFree RepleniSH, SoloCare Aqua, and Complete Moisture Plus. The SiHy materials evaluated were lotrafilcon A, lotrafilcon B, comfilcon A, galyfilcon A, and balafilcon A (BA). MPS-soaked lenses were placed on top of adherent HCEC. The effect of MPS dilutions (0.1 to 10% final concentration in medium) was also characterized. Cell viability, adhesion phenotype and caspase activation were studied after 24-h cell exposure. OFX released from lenses was determined using UV absorbance. Results A significant reduction in viability (between 30 to 50%) was observed with cells exposed to lenses soaked in ReNu and OFX. A significant downregulation of α3 and β1 integrins, with integrin expression ranging from 60% to 75% of control (cells with no lens), was also observed with OFX and ReNu-soaked lenses. With the exception of BA, all other lenses soaked in OFX resulted in significant caspase activation, whereby over 18% of cells stained positive for caspases. Minimal caspase activation was observed in cells exposed to ReNu and Solo soaked lenses. For both OFX and ReNu, exposing cells to at least a 5% dilution had a significant effect on viability and integrin expression. While Complete and Solo did not lead to reduction in viability, cells exposed to a 10% dilution showed reduced integrin expression down to less than 70% of control value. Comparing cell response to diluted MPS solutions and various MPS-soaked lenses showed that it is not possible to reliably use cell response to MPS dilution alone to assess MPS

  5. [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

  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. In vitro investigation of ultrasound-induced oxidative stress on human lens epithelial cells.

    PubMed

    Rwei, Patrick; Alex Gong, Cihun-Siyong; Luo, Li-Jyuan; Lin, Meng-Bo; Lai, Jui-Yang; Liu, Hao-Li

    2017-01-22

    The effect of ultrasound exposure on human lens epithelial cells (HLE-B3) was investigated in vitro, specifically on the generation of oxidative stress upon ultrasound application using various clinically-relevant settings. In addition to ultrasound-induced heat effects, oxidative stress has been recently proposed as one of the main mechanisms for ultrasound-induced effects on human cells. In this work, the levels of biocompatibility and generation of oxidative stress by exposure of ultrasound to HLE-B3 were evaluated quantitatively and qualitatively by the MTT assay, Live/Dead assay, reactive oxygen species (ROS) and intracellular calcium level. Oxidative stress induction is traditionally achieved through administrations of H2O2 and thus the administration of H2O2 was used as the positive control group for comparison herein. Concerning the administrations of H2O2 are considered invasive and may potentially have side effects, ultrasound as physical stimulation could be a safer and non-invasive method to induce similar oxidative stress environments. The effect of ultrasound on cell viability and induction of oxidative stress increases with ultrasound intensity. The result reveals that the continuous ultrasound has a positive impact on the oxidative stress levels but does negatively on the cell viability, as compared to the pulsed ultrasound. Furthermore, our work demonstrates that the exposure of 58 kPa continuous ultrasound without microbubbles can maintain acceptable cell viability and produce oxidative stress effects similar to the traditional administrations of H2O2. In summary, exposure of ultrasound can generate oxidative stress comparable to traditional administrations of H2O2. The effect of generating oxidative stress is adjustable through ultrasound parameters, including the pulsed or continuous wave, the intensity of ultrasound and addition of microbubbles.

  8. 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.

  9. The significance of the shape of the lens and capsular energy changes in accommodation

    PubMed Central

    Fisher, R. F.

    1969-01-01

    1. A method for the estimation of the energy released by the anterior part of the lens capsule during accommodation is described. This includes (i) A determination of the pressure required to distend the capsule by a standard volume. (ii) The calculation from the photographed lens profiles of the degree of capsular contraction which occurs when the lens changes from the unaccommodated to the accommodated form. (iii) Capsular volume changes in vitro are then related to the surface area changes calculated for the lens in vivo. 2. A correlation exists between the stored capsular energy per unit area or surface tension and the accommodation power of different species. The human lens capsule releases 1170 ergs/cm2 while the more spherical lenses of the cat and rabbit release 520 and 485 ergs/cm2 respectively for a 10% change in lens diameter. The amount of energy which can be stored depends on the degree of flatness of the lens and the volume of the anterior segment. The flatter the lens and the smaller the volume of the anterior segment, the greater the capsular surface tension. 3. The anterior surface of the human lens remains ellipsoidal throughout life. The changes of accommodation which occur in presbyopia may therefore be related to the lens profiles at various ages. It is found that a coefficient obtained by dividing the anterior volume of the lens by the 5th power of the equatorial radius of the lens modifies the degree of accommodation for a given change of lens diameter. 4. The loss of accommodation is proportional to the effective capsular surface energy until about the age of 45. The effective capsular surface energy can be defined as the energy which gives the same change in lens dioptric power per erg regardless of the lenticular profile changes which occur with age. It is obtained by multiplying capsular surface tension at a given age by a ratio. This is obtained by dividing the profile coefficient mentioned in paragraph 3 of the given lens, by the

  10. Closed-form approximations for two-dimensional groundwater age patterns in a fresh water lens.

    PubMed

    Greskowiak, Janek; Röper, Tania; Post, Vincent E A

    2013-01-01

    Simple closed-form approximations are presented for calculating the steady-state groundwater age distribution in two-dimensional vertical cross sections of idealized fresh water lenses overlying salt water, for aquifers that are vertically semi-infinite and of finite thickness. The approximations are developed on the basis of existing one-dimensional analytical solutions for travel-time calculation in fresh water lenses and approximate streamline formulations. The two-dimensional age distributions based on the closed-form solutions match convincingly with numerical simulations. As expected, notable deviations from the numerical solution are encountered at the groundwater flow divide and when submarine groundwater discharge occurs. Ratios of recharge over hydraulic conductivities are varied to explore how the magnitude of the deviations changes, and it is found that the approximate closed-form solutions perform well over a range of conditions found in natural systems.

  11. Assessing Age-Related Changes in the Biomechanical Properties of Rabbit Lens Using a Coaligned Ultrasound and Optical Coherence Elastography System

    PubMed Central

    Wu, Chen; Han, Zhaolong; Wang, Shang; Li, Jiasong; Singh, Manmohan; Liu, Chih-hao; Aglyamov, Salavat; Emelianov, Stanislav; Manns, Fabrice; Larin, Kirill V.

    2015-01-01

    Purpose. To evaluate the capability of a novel, coaligned focused ultrasound and phase-sensitive optical coherence elastography (US-OCE) system to assess age-related changes in biomechanical properties of the crystalline lens in situ. Methods. Low-amplitude elastic deformations in young and mature rabbit lenses were measured by an US-OCE system consisting of a spectral-domain optical coherence tomography (OCT) system coaligned with a focused ultrasound system used to produce a transient force on the lens surface. Uniaxial compressional tests were used to validate the OCE data. Results. The OCE measurements showed that the maximum displacements of the young rabbit lenses were significantly larger than those of the mature lenses, indicating a gradual increase of the lens stiffness with age. Temporal analyses of the displacements also demonstrate a similar trend of elastic properties in these lenses. The stress-strain measurements using uniaxial mechanical tests confirmed the results obtained by the US-OCE system. Conclusions. The results demonstrate that the US-OCE system can be used for noninvasive analysis and quantification of lens biomechanical properties in situ and possibly in vivo. PMID:25613945

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. In vitro ultraviolet–induced damage in human corneal, lens, and retinal pigment epithelial cells

    PubMed Central

    Youn, Hyun-Yi; Sivak, Jacob G.; Jones, Lyndon W.

    2011-01-01

    Purpose The purpose was to develop suitable in vitro methods to detect ocular epithelial cell damage when exposed to UV radiation, in an effort to evaluate UV-absorbing ophthalmic biomaterials. Methods Human corneal epithelial cells (HCEC), lens epithelial cells (HLEC), and retinal pigment epithelial cells (ARPE-19) were cultured and Ultraviolet A/Ultraviolet B (UVA/UVB) blocking filters and UVB-only blocking filters were placed between the cells and a UV light source. Cells were irradiated with UV radiations at various energy levels with and without filter protections. Cell viability after exposure was determined using the metabolic dye alamarBlue and by evaluating for changes in the nuclei, mitochondria, membrane permeability, and cell membranes of the cells using the fluorescent dyes Hoechst 33342, rhodamine 123, calcein AM, ethidium homodimer-1, and annexin V. High-resolution images of the cells were taken with a Zeiss 510 confocal laser scanning microscope. Results The alamarBlue assay results of UV-exposed cells without filters showed energy level-dependent decreases in cellular viability. However, UV treated cells with 400 nm LP filter protection showed the equivalent viability to untreated control cells at all energy levels. Also, UV irradiated cells with 320 nm LP filter showed lower cell viability than the unexposed control cells, yet higher viability than UV-exposed cells without filters in an energy level-dependent manner. The confocal microscopy results also showed that UV radiation can cause significant dose-dependent degradations of nuclei and mitochondria in ocular cells. The annexin V staining also showed an increased number of apoptotic cells after UV irradiation. Conclusions The findings suggest that UV-induced HCEC, HLEC, and ARPE-19 cell damage can be evaluated by bioassays that measure changes in the cell nuclei, mitochondria, cell membranes, and cell metabolism, and these assay methods provide a valuable in vitro model for evaluating the

  17. Apparent intermediate K conductance channel hyposmotic activation in human lens epithelial cells.

    PubMed

    Lauf, Peter K; Misri, Sandeep; Chimote, Ameet A; Adragna, Norma C

    2008-03-01

    This study explores the nature of K fluxes in human lens epithelial cells (LECs) in hyposmotic solutions. Total ion fluxes, Na-K pump, Cl-dependent Na-K-2Cl (NKCC), K-Cl (KCC) cotransport, and K channels were determined by 85Rb uptake and cell K (Kc) by atomic absorption spectrophotometry, and cell water gravimetrically after exposure to ouabain +/- bumetanide (Na-K pump and NKCC inhibitors), and ion channel inhibitors in varying osmolalities with Na, K, or methyl-d-glucamine and Cl, sulfamate, or nitrate. Reverse transcriptase polymerase chain reaction (RT-PCR), Western blot analyses, and immunochemistry were also performed. In isosmotic (300 mosM) media approximately 90% of the total Rb influx occurred through the Na-K pump and NKCC and approximately 10% through KCC and a residual leak. Hyposmotic media (150 mosM) decreased K(c) by a 16-fold higher K permeability and cell water, but failed to inactivate NKCC and activate KCC. Sucrose replacement or extracellular K to >57 mM, but not Rb or Cs, in hyposmotic media prevented Kc and water loss. Rb influx equaled Kc loss, both blocked by clotrimazole (IC50 approximately 25 microM) and partially by 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) inhibitors of the IK channel KCa3.1 but not by other K channel or connexin hemichannel blockers. Of several anion channel blockers (dihydro-indenyl)oxy]alkanoic acid (DIOA), 4-2(butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl)oxybutyric acid (DCPIB), and phloretin totally or partially inhibited Kc loss and Rb influx, respectively. RT-PCR and immunochemistry confirmed the presence of KCa3.1 channels, aside of the KCC1, KCC2, KCC3 and KCC4 isoforms. Apparently, IK channels, possibly in parallel with volume-sensitive outwardly rectifying Cl channels, effect regulatory volume decrease in LECs.

  18. Sustained-release genistein from nanostructured lipid carrier suppresses human lens epithelial cell growth

    PubMed Central

    Liu, Jin-Lu; Zhang, Wen-Ji; Li, Xue-Dong; Yang, Na; Pan, Wei-San; Kong, Jun; Zhang, Jin-Song

    2016-01-01

    AIM To design and investigate the efficacy of a modified nanostructured lipid carrier loaded with genistein (Gen-NLC) to inhibit human lens epithelial cells (HLECs) proliferation. METHODS Gen-NLC was made by melt emulsification method. The morphology, particle size (PS), zeta potentials (ZP), encapsulation efficiency (EE) and in vitro release were characterized. The inhibition effect of nanostructured lipid carrier (NLC), genistein (Gen) and Gen-NLC on HLECs proliferation was evaluated by cell counting kit-8 (CCK-8) assay, gene and protein expression of the proliferation marker Ki67 were evaluated with real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence analyses. RESULTS The mean PS of Gen-NLC was 80.12±1.55 nm with a mean polydispersity index of 0.11±0.02. The mean ZP was -7.14±0.38 mV and the EE of Gen in the nanoparticles was 92.3%±0.73%. Transmission electron microscopy showed that Gen-NLC displayed spherical-shaped particles covered by an outer-layer structure. In vitro release experiments demonstrated a prolonged drug release for 72h. The CCK-8 assay results showed the NLC had no inhibitory effect on HLECs and Gen-NLC displayed a much more prominent inhibitory effect on cellular growth compared to Gen of the same concentration. The mRNA and protein expression of Ki67 in LECs decreased significantly in Gen-NLC group. CONCLUSION Sustained drug release by Gen-NLCs may impede HLEC growth. PMID:27275415

  19. Aging and financial planning for retirement: interdisciplinary influences viewed through a cross-cultural lens.

    PubMed

    Hershey, Douglas A; Henkens, Kene; Van Dalen, Hendrik P

    2010-01-01

    Current theoretical models support the existence of interactions between the individual and socio-environmental forces when it comes to the formation and enactment of life plans (Friedman & Scholnick, 1997; Shanahan & Elder, 2002). In this investigation, we examine the social, economic, and psychological forces that impact financial planning for retirement. The collective force of these three broad sets of influences was examined from developmental and cross-cultural perspectives, among respondents from two countries with very different retirement financing systems. Participants were 419 American and 556 Dutch working adults, 25-64 years of age. Path analysis models were created to examine differences in planning associated with age and national origin. Compared to younger individuals, older respondents in both countries were more involved in nearly all aspects of the financial planning process. Differences across cultures were also observed in the social support mechanisms that underlie planning and the impact economic forces have on perceptions of saving adequacy. The discussion focuses on the value of developing interdisciplinary theoretical models of planning, and how such models can inform the development of savings-oriented intervention and public policy initiatives.

  20. Insect-Human Hybrid Eye (IHHE): an adaptive optofluidic lens combining the structural characteristics of insect and human eyes.

    PubMed

    Wei, Kang; Zeng, Hansong; Zhao, Yi

    2014-09-21

    Insect compound eyes and human camera eyes are two exquisite optical systems created by nature. The compound eye boasts an angle of view (AOV) up to 180° thanks to its hemispherical arrangement of hundreds of prime microscale lenses. The camera eye, on the other hand, can change shape to focus on objects at various depths, yet accepts light within a smaller AOV. Imitations of either imaging system have been abundant but with limited success. Here, we describe a reconfigurable polymeric optofluidic device that combines the architectural merits of both vision mechanisms, featuring a large AOV (up to 120°) with adaptive focusing capabilities (from 0 to 275 diopter (D)). This device consists of bi-layered microfluidics: an array of millimeter-sized fluidic lenses is integrated into the top layer and arranged on an elastomeric membrane embedded within the bottom layer. The membrane can be deformed from a planar surface into a series of dome-shaped geometries, rearranging individual fluidic lenses in desired curvilinear layouts. Meanwhile, each fluidic lens can vary its radius of curvature for a monocular depth sensation. Such a design presents a new perspective of tunable optofluidics for a broad range of applications, such as robotic vision and medical laparoendoscopy, where adaptive focalization with a large viewing angle is a clear advantage.

  1. 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.

  2. Acanthamoeba polyphaga Strain Age and Method of Cyst Production Influence the Observed Efficacy of Therapeutic Agents and Contact Lens Disinfectants

    PubMed Central

    Hughes, Reanne; Heaselgrave, Wayne; Kilvington, Simon

    2003-01-01

    The effects of age in culture and the type of medium used for induction of Acanthamoeba polyphaga (Ros) cysts on susceptibilities to polyhexamethylene biguanide (PHMB; 3 μg/ml), chlorhexidine digluconate (30 μg/ml), myristamidopropyl dimethylamine (20 μg/ml), H2O2 (3%), and two multipurpose contact lens solutions (MPS-1 and MPS-2, based on 1 μg of PHMB per ml) were examined. Strain Ros-02 was cryopreserved on isolation in 1991, while strain Ros-91 had been in continuous axenic culture. Significant differences in susceptibilities to the disinfectants were found depending on the medium used for cyst preparation and the age of the test strain, with Ros-02 generally being more resistant. For example, the killing of Ros-91 cysts produced from an axenic culture of trophozoites in the presence of 50 mM MgCl2 by MPS-2 was 4 logs, but the killing of Ros-02 by MPS-2 was only 2 logs (P < 0.05) and killing of both strains with cysts obtained from monoxenic cultures with Escherichia coli was only 1 log (P < 0.001). Assays repeated with different batches of the various cyst types gave consistent results. A batch of Ros-91 cysts stored at 4°C and tested over an 8-week period with MPS-1 showed progressively increasing susceptibility to disinfection, although there was no loss of viability during storage (P < 0.01). These observations have important implications for the standardization and interpretation of Acanthamoeba disinfectant and therapeutic agent testing. PMID:14506012

  3. Picturing neuroscience research through a human rights lens: imaging first-episode schizophrenic treatment-naive individuals.

    PubMed

    Eijkholt, Marleen; Anderson, James A; Illes, Judy

    2012-01-01

    In this paper we examine imaging research involving first-episode schizophrenic treatment-naive individuals (FESTNIs) through a legal human rights lens; in particular, the lens of the Additional Protocol to the Convention on Human Rights and Biomedicine Concerning Biomedical Research. We identify a number of ethical and legal hot spots highlighted by the Protocol, and offer a series of recommendations designed to ensure the human rights compatibility of this research. Subsequently, we argue that the lack of reporting on design elements related to ethical concerns frustrates commitments at the heart of the human rights approach, namely, transparency and openness to international scrutiny. To redress this problem, we introduce two norms for the first time: ethical transparency, and ethical reproducibility. When concluding, we offer a set of reporting guidelines designed to operationalize these norms in the context of imaging research involving FESTNIs. Though we will not make this case here, we believe that parallel reporting guidelines should be incorporated into other areas of research involving human subjects.

  4. The spherical aberration of the crystalline lens of the human eye.

    PubMed

    Smith, G; Cox, M J; Calver, R; Garner, L F

    2001-01-15

    The in vivo spherical aberration of the lenses of 26 subjects was estimated from the measured total aberration of the eye and that predicted from the measured shape of the anterior corneal surface. Since it was only possible to estimate the aberration contribution from the posterior corneal surface, its value led to an uncertainty in the final aberration level of the lens. For all the subjects and for a wide range of possible aberration levels at the posterior corneal surface, the spherical aberration of the relaxed lens was found to be negative.

  5. Measurements of elastic modulus for human anterior lens capsule with atomic force microscopy: the effect of loading force.

    PubMed

    Tsaousis, Konstantinos T; Karagiannidis, Panagiotis G; Kopsachilis, Nikolaos; Symeonidis, Chrysanthos; Tsinopoulos, Ioannis T; Karagkiozaki, Varvara; Lamprogiannis, Lampros P; Logothetidis, Stergios

    2014-06-01

    The purpose of the study was to appraise the effect of loading force magnitude on the determination of the elastic modulus of the anterior lens capsule through atomic force microscopy. Four human anterior lens capsules taken during phacoemulsification cataract surgery were studied, free of epithelial cells, with atomic force microscopy. For the experiment, five different indentation loading forces were applied to near areas of the specimen. Experimental data was exported and analyzed according to the Hertz model to obtain the Young's modulus with regards to the elastic behavior of the material. Force-distance curves were acquired by applying a load of 2, 5, 10, 20 and 30 nN. When examining the results it was evident that determination of Young's modulus of the anterior lens capsule is dependent on the loading force concerning the examined range. Loading forces of 10 and 20 nN led to results without significant difference (p > 0.05) and more reproducible (coefficients of variation 12.4 and 11.7 %, respectively).

  6. Fabry lens.

    NASA Technical Reports Server (NTRS)

    Michlovic, J.

    1972-01-01

    Discussion of the properties, operation, and applications of the Fabry lens. As used in stellar photometry, a Fabry lens is nothing more than a simple converging lens inserted into the optical train of a photometer to construct an image of the objective on the photomultiplier cathode. The thereby derived advantages are reviewed, and some techniques designed to maximize these advantages are outlined.

  7. Human protein aging: modification and crosslinking through dehydroalanine and dehydrobutyrine intermediates.

    PubMed

    Wang, Zhen; Lyons, Brian; Truscott, Roger J W; Schey, Kevin L

    2014-04-01

    Nonenzymatic post-translational modification (PTM) of proteins is a fundamental molecular process of aging. The combination of various modifications and their accumulation with age not only affects function, but leads to crosslinking and protein aggregation. In this study, aged human lens proteins were examined using HPLC-tandem mass spectrometry and a blind PTM search strategy. Multiple thioether modifications of Ser and Thr residues by glutathione (GSH) and its metabolites were unambiguously identified. Thirty-four of 36 sites identified on 15 proteins were found on known phosphorylation sites, supporting a mechanism involving dehydroalanine (DHA) and dehydrobutyrine (DHB) formation through β-elimination of phosphoric acid from phosphoserine and phosphothreonine with subsequent nucleophilic attack by GSH. In vitro incubations of phosphopeptides demonstrated that this process can occur spontaneously under physiological conditions. Evidence that this mechanism can also lead to protein-protein crosslinks within cells is provided where five crosslinked peptides were detected in a human cataractous lens. Nondisulfide crosslinks were identified for the first time in lens tissue between βB2- & βB2-, βA4- & βA3-, γS- & βB1-, and βA4- & βA4-crystallins and provide detailed structural information on in vivo crystallin complexes. These data suggest that phosphoserine and phosphothreonine residues represent susceptible sites for spontaneous breakdown in long-lived proteins and that DHA- and DHB-mediated protein crosslinking may be the source of the long-sought after nondisulfide protein aggregates believed to scatter light in cataractous lenses. Furthermore, this mechanism may be a common aging process that occurs in long-lived proteins of other tissues leading to protein aggregation diseases.

  8. Human protein aging: modification and crosslinking through dehydroalanine and dehydrobutyrine intermediates

    PubMed Central

    Wang, Zhen; Lyons, Brian; Truscott, Roger J W; Schey, Kevin L

    2014-01-01

    Nonenzymatic post-translational modification (PTM) of proteins is a fundamental molecular process of aging. The combination of various modifications and their accumulation with age not only affects function, but leads to crosslinking and protein aggregation. In this study, aged human lens proteins were examined using HPLC–tandem mass spectrometry and a blind PTM search strategy. Multiple thioether modifications of Ser and Thr residues by glutathione (GSH) and its metabolites were unambiguously identified. Thirty-four of 36 sites identified on 15 proteins were found on known phosphorylation sites, supporting a mechanism involving dehydroalanine (DHA) and dehydrobutyrine (DHB) formation through β-elimination of phosphoric acid from phosphoserine and phosphothreonine with subsequent nucleophilic attack by GSH. In vitro incubations of phosphopeptides demonstrated that this process can occur spontaneously under physiological conditions. Evidence that this mechanism can also lead to protein–protein crosslinks within cells is provided where five crosslinked peptides were detected in a human cataractous lens. Nondisulfide crosslinks were identified for the first time in lens tissue between βB2- & βB2-, βA4- & βA3-, γS- & βB1-, and βA4- & βA4-crystallins and provide detailed structural information on in vivo crystallin complexes. These data suggest that phosphoserine and phosphothreonine residues represent susceptible sites for spontaneous breakdown in long-lived proteins and that DHA- and DHB-mediated protein crosslinking may be the source of the long-sought after nondisulfide protein aggregates believed to scatter light in cataractous lenses. Furthermore, this mechanism may be a common aging process that occurs in long-lived proteins of other tissues leading to protein aggregation diseases. PMID:24134651

  9. 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

  10. Extremely Low Frequency Magnetic Fields Do Not Induce DNA Damage in Human Lens Epithelial Cells In Vitro.

    PubMed

    Zhu, Kan; Lv, Ye; Cheng, Qian; Hua, Jianing; Zeng, Qunli

    2016-05-01

    Non-ionizing radiations, e.g., radiofrequency electromagnetic fields, could induce DNA damage and oxidative stress in human lens epithelial cells (LECs) which can be early events in cataractogenesis. Extremely low frequency magnetic fields (ELF MF) as another common form of man-made electromagnetic fields has been considered as suspected human carcinogen by International Agency for Research on Cancer (IARC) and become a focus that people play more and more attentions to. This study aimed to determine whether ELF MF can induce DNA damage in cultured human LECs at a relatively low intensity. Human LECs were exposed or sham-exposed to a 50 Hz ELF MF which produced by a well-designed exposure system at the intensity of 0.4 mT. DNA damage in human LECs was examined by the phosphorylated form of histone variant H2AX (γH2AX) foci formation assay and further explored with western blot, flow cytometry, and alkaline comet assay. Immunofluorescence analysis showed that 0.4 mT ELF MF did not significantly increase γH2AX foci formation in human LECs after 2, 6, 12, 24, or 48 hr exposure. No significant differences had been detected in γH2AX expression level between the ELF MF- and sham-exposure groups, while no obvious chromosomal DNA fragmentation was detected by alkaline comet assay after ELF MF exposure. The results indicate an absence of genotoxicity in ELF MF-exposed human epithelial cells and do not support the hypothesis that environmental ELF MF might be causally led to genomic instability via chromosomal damage response processes. Neither short nor long term continuous exposure to 50 Hz ELF MF at 0.4 mT could induce DNA damage in human lens epithelial cells in vitro.

  11. 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.

  12. Ionizing Irradiation Not Only Inactivates Clonogenic Potential in Primary Normal Human Diploid Lens Epithelial Cells but Also Stimulates Cell Proliferation in a Subset of This Population

    PubMed Central

    Fujimichi, Yuki; Hamada, Nobuyuki

    2014-01-01

    Over the past century, ionizing radiation has been known to induce cataracts in the crystalline lens of the eye, but its mechanistic underpinnings remain incompletely understood. This study is the first to report the clonogenic survival of irradiated primary normal human lens epithelial cells and stimulation of its proliferation. Here we used two primary normal human cell strains: HLEC1 lens epithelial cells and WI-38 lung fibroblasts. Both strains were diploid, and a replicative lifespan was shorter in HLEC1 cells. The colony formation assay demonstrated that the clonogenic survival of both strains decreases similarly with increasing doses of X-rays. A difference in the survival between two strains was actually insignificant, although HLEC1 cells had the lower plating efficiency. This indicates that the same dose inactivates the same fraction of clonogenic cells in both strains. Intriguingly, irradiation enlarged the size of clonogenic colonies arising from HLEC1 cells in marked contrast to those from WI-38 cells. Such enhanced proliferation of clonogenic HLEC1 cells was significant at ≥2 Gy, and manifested as increments of ≤2.6 population doublings besides sham-irradiated controls. These results suggest that irradiation of HLEC1 cells not only inactivates clonogenic potential but also stimulates proliferation of surviving uniactivated clonogenic cells. Given that the lens is a closed system, the stimulated proliferation of lens epithelial cells may not be a homeostatic mechanism to compensate for their cell loss, but rather should be regarded as abnormal. This is because these findings are consistent with the early in vivo evidence documenting that irradiation induces excessive proliferation of rabbit lens epithelial cells and that suppression of lens epithelial cell divisions inhibits radiation cataractogenesis in frogs and rats. Thus, our in vitro model will be useful to evaluate the excessive proliferation of primary normal human lens epithelial cells that

  13. Telescopic vision contact lens

    NASA Astrophysics Data System (ADS)

    Tremblay, Eric J.; Beer, R. Dirk; Arianpour, Ashkan; Ford, Joseph E.

    2011-03-01

    We present the concept, optical design, and first proof of principle experimental results for a telescopic contact lens intended to become a visual aid for age-related macular degeneration (AMD), providing magnification to the user without surgery or external head-mounted optics. Our contact lens optical system can provide a combination of telescopic and non-magnified vision through two independent optical paths through the contact lens. The magnified optical path incorporates a telescopic arrangement of positive and negative annular concentric reflectors to achieve 2.8x - 3x magnification on the eye, while light passing through a central clear aperture provides unmagnified vision.

  14. Sigma 1 receptor stimulation protects against oxidative damage through suppression of the ER stress responses in the human lens.

    PubMed

    Wang, Lixin; Eldred, Julie A; Sidaway, Peter; Sanderson, Julie; Smith, Andrew J O; Bowater, Richard P; Reddan, John R; Wormstone, I Michael

    2012-01-01

    Stimulation of sigma-1 receptors is reported to protect against oxidative stress. The present study uses cells and tissue from the human lens to elucidate the relationship between the sigma 1 receptor, ER stress and oxidative stress-induced damage. Exposure of the human lens cell line FHL124 to increasing concentrations of H(2)O(2) led to reduced cell viability and increased apoptosis. In response to 30 μM H(2)O(2), levels of the ER stress proteins BiP, ATF6 and pEIF2α were significantly increased within 4h of exposure. Expression of the sigma 1 receptor was markedly increased in response to H(2)O(2). Application of 10 and 30 μM (+)-pentazocine, a sigma 1 receptor agonist, significantly inhibited the H(2)O(2) induced cell death. (+)-Pentazocine also suppressed the oxidative stress induced reduction of pro-caspase 12 and suppressed the induction of the ER stress proteins BiP and EIF2α. When applied to cultured human lenses, (+)-pentazocine protected against apoptotic cell death, LDH release and against H(2)O(2) induced opacification. These data demonstrate that stimulation of the sigma 1 receptor provides significant protection from oxidative damage and is, therefore, a putative therapeutic approach to delay the onset of diseases that may be triggered by oxidative damage, including cataract formation.

  15. 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

  16. Intraocular lens fabrication

    DOEpatents

    Salazar, Mike A.; Foreman, Larry R.

    1997-01-01

    This invention describes a method for fabricating an intraocular lens made rom clear Teflon.TM., Mylar.TM., or other thermoplastic material having a thickness of about 0.025 millimeters. These plastic materials are thermoformable and biocompatable with the human eye. The two shaped lenses are bonded together with a variety of procedures which may include thermosetting and solvent based adhesives, laser and impulse welding, and ultrasonic bonding. The fill tube, which is used to inject a refractive filling material is formed with the lens so as not to damage the lens shape. A hypodermic tube may be included inside the fill tube.

  17. Intraocular lens fabrication

    DOEpatents

    Salazar, M.A.; Foreman, L.R.

    1997-07-08

    This invention describes a method for fabricating an intraocular lens made from clear Teflon{trademark}, Mylar{trademark}, or other thermoplastic material having a thickness of about 0.025 millimeters. These plastic materials are thermoformable and biocompatable with the human eye. The two shaped lenses are bonded together with a variety of procedures which may include thermosetting and solvent based adhesives, laser and impulse welding, and ultrasonic bonding. The fill tube, which is used to inject a refractive filling material is formed with the lens so as not to damage the lens shape. A hypodermic tube may be included inside the fill tube. 13 figs.

  18. 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.

  19. Non-destructive analysis of the conformational changes in human lens lipid and protein structures of the immature cataracts associated with glaucoma

    NASA Astrophysics Data System (ADS)

    Lin, Shan-Yang; Li, Mei-Jane; Liang, Run-Chu; Lee, Shui-Mei

    1998-09-01

    Previous study has supposed a possible mechanism of exacerbating cataract formation in cataractous human lens capsules induced by hypertension or glaucoma. To clarify the glaucoma-induced cataract formation of the eyes lens, changes in the human lens lipid and protein structures of immature cataractous patients with or without glaucoma were investigated. Two normal lenses, ten immature cataractous lenses without any complication and four immature cataractous lenses with glaucoma were used after surgical operation. Each de-capsulated human lens sample was sliced with a number 15 surgical blade. The intact nuclear lens regions were used for non-destructive analysis. The lens lipid and protein structures, as well as compositions of these lens samples, were determined using a Fourier transform infrared (FTIR) microspectroscopy with second-derivative, de-convolution and curve-fitting methods. The results indicate that the IR spectrum of glaucomatous lenses appeared as a shoulder only at 2853 cm -1, thus the composition of the symmetric CH 2 stretching band at 2853 (2852) cm -1 decreased more significantly in glaucomatous lens to only one half of that in normal and immature cataractous lenses. The composition of the asymmetric CH 3 stretching band at 2965 cm -1 for normal lens decreases markedly from 32 to 20% for immature cataractous lenses with or without glaucoma. The compositional ratio of component at 2965 cm -1 to component at 2928 (2930) cm -1 for normal lenses was about 0.702, and that ratio for cataractous lenses without glaucoma was 0.382 but for glaucomatous lenses was 0.377. The maximum peak position of amide I band for IR spectra of the normal lens, immature cataractous lenses without complications or glaucomatous lenses appeared respectively at 1632, 1630 or 1622 cm -1, assigned to β sheet structure. A marked difference in peak intensity of amide I band for the normal lenses and immature cataractous human lenses with or without glaucoma was observed. The

  20. 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.

  1. Refractive power and biometric properties of the nonhuman primate isolated crystalline lens.

    PubMed

    Borja, David; Manns, Fabrice; Ho, Arthur; Ziebarth, Noel M; Acosta, Ana Carolina; Arrieta-Quintera, Esdras; Augusteyn, Robert C; Parel, Jean-Marie

    2010-04-01

    Purpose. To characterize the age dependence of shape, refractive power, and refractive index of isolated lenses from nonhuman primates. Methods. Measurements were performed on ex vivo lenses from cynomolgus monkeys (cyno: n = 120; age, 2.7-14.3 years), rhesus monkeys (n = 61; age, 0.7-13.3 years), and hamadryas baboons (baboon: n = 16; age, 1.7-27.3 years). Lens thickness, diameter, and surface curvatures were measured with an optical comparator. Lens refractive power was measured with a custom optical system based on the Scheiner principle. The refractive contributions of the gradient, the surfaces, and the equivalent refractive index were calculated with optical ray-tracing software. The age dependence of the optical and biometric parameters was assessed. Results. Over the measured age range isolated lens thickness decreased (baboon: -0.04, cyno: -0.05, and rhesus: -0.06 mm/y) and equatorial diameter increased (logarithmically for the baboon and rhesus, and linearly for cyno: 0.07 mm/y). The isolated lens surfaces flattened and the corresponding refractive power from the surfaces decreased with age (-0.33, -0.48, and -0.68 D/y). The isolated lens equivalent refractive index decreased (only significant for the baboon, -0.001 D/y), and as a result the total isolated lens refractive power decreased with age (baboon: -1.26, cyno: -0.97, and rhesus: -1.76 D/y). Conclusions. The age-dependent trends in the optical and biometric properties, growth, and aging, of nonhuman primate lenses are similar to those of the pre-presbyopic human lens. As the lens ages, the decrease in refractive contributions from the gradient refractive index causes a rapid age-dependent decrease in maximally accommodated lens refractive power.

  2. 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.

  3. 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

  4. Phycocyanin may suppress D-galactose-induced human lens epithelial cell apoptosis through mitochondrial and unfolded protein response pathways.

    PubMed

    Ou, Yu; Yuan, Zhijun; Li, Kepeng; Yang, Xuegan

    2012-11-23

    Apoptosis of lens epithelial cell (LEC) plays an important role in cataract formation, and its prevention may be one of the therapeutic strategies in treating cataract. This study used human lens epithelial cell (hLEC) line SRA01/04 to investigate the protective effect and mechanism of phycocyanin on glactose-induced apoptosis in hLEC. hLECs were cultured in D/F(12)-10% FBS medium containing 125mM d-galactose with or without phycocyanin. Cell viability was assessed by methylthiazol tetrazolium (MTT) assay. Cell apoptosis was elevated with Wright-Giemsa staining, AO/EB double staining, and DNA fragmentation assay. Mitochondrial apoptosis-associated molecules and unfolded protein response-associated molecules from cultured SRA01/04 cells were quantified using protein blot analysis. The results demonstrated that phycocyanin suppressed SRA01/04 cells' morphologic changes and apoptosis induced by d-galactose, inhibited the expression and activation of caspase 3, alternated the Bax/Bcl-2 ratio, and down-regulated the level of p53, GRP78, and CHOP in d-galactose-treated SRA01/04 cells. These results suggest that phycocyanin might suppress d-galactose-induced hLEC apoptosis through two pathways: mitochondrial pathway, involving p53 and Bcl-2 family protein expression, and unfolded protein response pathway, involving GRP78 and CHOP expression.

  5. Enhanced cellular uptake and anti-proliferating effect of chitosan hydrochlorides modified genistein loaded NLC on human lens epithelial cells.

    PubMed

    Zhang, Wenji; Liu, Jinlu; Zhang, Qi; Li, Xuedong; Yu, Shihui; Yang, Xinggang; Kong, Jun; Pan, Weisan

    2014-08-25

    This study was attempted to increase the cellular uptake of developed genistein loaded nanostructured lipid carriers (NLC) into human lens epithelial (HLE) cells by chitosan hydrochlorides coatings when applied in post lens capsule (PCO) treatment, and to provide further understanding of the uptake and anti-proliferation mechanisms inside. NLCs were produced using melt-emulsification method and were subsequently coated with chitosan hydrochlorides by adsorption. The uptake of various particle sizes were evaluated and visualized by confocal laser scanning microscopy (CLSM), showing a size-dependent manner. The uptake of NLC was proved to be endocytosed in an energy dependent and clathrin-mediated endocytosis to HLE cells by the decrease in uptake at lower temperature, when pre-saturated by blank NLC and in the presence of NaN3 and sucrose. CH coating improved the uptake percentage of NLC irrespective of the particle size, without influencing the uptake mechanism. Cell apoptosis was tested using PI and Annexin V-FITC/PI staining, followed by flow cytometer analysis. Higher anti-proliferation effect was observed for CH-NLC in inhibiting the growth of HLE cells by causing more apoptosis. Results above indicate that GEN-NLC surface modified by chitosan hydrochlorides could enhance the trans-cellular performance and anti-proliferating effect as PCO therapy.

  6. 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.

  7. Responsiveness of the National Eye Institute Visual Function Questionnaire to Progression to Advanced Age-Related Macular Degeneration, Vision Loss, and Lens Opacity

    PubMed Central

    2006-01-01

    Objective To describe the ability of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) to detect meaningful change over time (responsiveness) to the primary Age-Related Eye Disease Study outcomes. Methods The 25-item NEI-VFQ plus appendix was administered at 2 visits at 1- to 4-year intervals to 4119 participants in the Age-Related Eye Disease Study. Events evaluated were progression to advanced age-related macular degeneration (AMD), visual acuity (VA) loss of at least 15 letters, and lens opacity progression. Responsiveness was measured by the t statistic, effect size (ES), responsiveness statistic, and area under the receiver operating characteristic curve. Variance components were used to estimate the contributions of events to variability of the NEI-VFQ score. Results Overall NEI-VFQ score was responsive to AMD progression (t = 14.0; P<.001; ES=0.81) and VA (t = 16.2; P<.001; ES=0.74). Mean changes ranged from 11 to 25 points for the subscales of general vision, near and distance activities, social functioning, mental health, role difficulties, dependency, and driving. The NEI-VFQ was unresponsive to lens opacity progression, although when the event occurred in the eye with the best vision at the first administration, the lens opacity ES was moderate for the color vision (ES = 0.62) and driving subscales (ES=0.66). Progression to advanced AMD and VA loss contributed significantly to the variation in the mean difference in overall VFQ score. Conclusions Changes in the NEI-VFQ overall and subscale scores of 10 points or more are associated with clinically significant changes in vision and AMD. This finding may assist the design of interventional studies of AMD and VA loss that include the NEI-VFQ as an outcome measure. PMID:16157800

  8. Objective lens

    NASA Technical Reports Server (NTRS)

    Olczak, Eugene G. (Inventor)

    2011-01-01

    An objective lens and a method for using same. The objective lens has a first end, a second end, and a plurality of optical elements. The optical elements are positioned between the first end and the second end and are at least substantially symmetric about a plane centered between the first end and the second end.

  9. Automated laser-scanning-microbeam fluorescence/Raman image analysis of human lens with multichannel detection: evidence for metabolic production of a green fluorophor.

    PubMed Central

    Yu, N T; Cai, M Z; Ho, D J; Kuck, J F

    1988-01-01

    A laser-microprobe fluorescence/Raman spectrometer with a 700-channel detector has been constructed and applied to the collection of data on the distribution of a green fluorophor throughout the exposed area of a human lens sectioned along the visual axis. The area (approximately 6.5 X 9.5 mm) covering the lens section was scanned automatically by the microprobe programmed to measure the fluorescence intensity at 1200 data points. The spectrometer output was accumulated in a microcomputer and displayed as a three-dimensional perspective view showing the fluorescence intensity at each point on the grid. The method permits the precise and detailed mapping at high resolution of the spatial distribution of a fluorophor or Raman-emissive constituent in a plane of the frozen lens to give results not obtainable by any other feasible procedure. The green fluorophor (441.6 nm, excitation wavelength; 520 nm, peak emission wavelength) has a distribution indicating a metabolic rather than a photochemical mode of production. Moreover, the lower level of fluorophor in the anterior segment suggests the existence of mechanisms in the anterior cortex (including the epithelium) that reduce significantly the accumulation of fluorophor. Such distribution studies are invaluable in clarifying metabolic interrelationships among the different zones of the lens, including especially photochemical reactions postulated to involve the effect of daylight on the lens in human subjects. Images PMID:3422407

  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. Why do lie-catchers fail? A lens model meta-analysis of human lie judgments.

    PubMed

    Hartwig, Maria; Bond, Charles F

    2011-07-01

    Decades of research has shown that people are poor at detecting lies. Two explanations for this finding have been proposed. First, it has been suggested that lie detection is inaccurate because people rely on invalid cues when judging deception. Second, it has been suggested that lack of valid cues to deception limits accuracy. A series of 4 meta-analyses tested these hypotheses with the framework of Brunswik's (1952) lens model. Meta-Analysis 1 investigated perceived cues to deception by correlating 66 behavioral cues in 153 samples with deception judgments. People strongly associate deception with impressions of incompetence (r = .59) and ambivalence (r = .49). Contrary to self-reports, eye contact is only weakly correlated with deception judgments (r = -.15). Cues to perceived deception were then compared with cues to actual deception. The results show a substantial covariation between the 2 sets of cues (r = .59 in Meta-Analysis 2, r = .72 in Meta-Analysis 3). Finally, in Meta-Analysis 4, a lens model analysis revealed a very strong matching between behaviorally based predictions of deception and behaviorally based predictions of perceived deception. In conclusion, contrary to previous assumptions, people rarely rely on the wrong cues. Instead, limitations in lie detection accuracy are mainly attributable to weaknesses in behavioral cues to deception. The results suggest that intuitive notions about deception are more accurate than explicit knowledge and that lie detection is more readily improved by increasing behavioral differences between liars and truth tellers than by informing lie-catchers of valid cues to deception.

  14. Fresnel Lens

    NASA Technical Reports Server (NTRS)

    Watson, Michael D.; Scott, Steve; Lamb, David; Zimmerman, Joe E. (Technical Monitor)

    2001-01-01

    Fresnel lenses span the full range of sizes from lens a few micrometers in diameter to lens several meters in diameter. These lenses are utilized in various fields including optical communication, theatrical lighting, office equipment, video entertainment systems, solar concentrators, and scientific research instruments. These lenses function either as diffractive or refractive optical elements depending on the geometrical feature size of the lens. The basic functions of these lenses is described followed by an overview of fabrication methods. A summary of applications is then provided illustrating the rich variety of applications for which fresnel lenses may be designed to fulfill.

  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. Virtual human technology: capturing sex, race, and age influences in individual pain decision policies.

    PubMed

    Hirsh, Adam T; Alqudah, Ashraf F; Stutts, Lauren A; Robinson, Michael E

    2008-11-15

    Pain assessment is subject to bias due to characteristics of the individual in pain and of the observing person. Few research studies have examined pain assessment biases in an experimental setting. This study employs innovative virtual human technology to achieve greater experimental control. A lens model design was used to capture decision-making policies at the idiographic and nomothetic level. Seventy-five undergraduates viewed virtual humans (VH) that varied in sex, race, age, and pain expression. Participants provided computerized ratings with Visual Analogue Scales on the VH's pain intensity, pain unpleasantness, negative mood, coping, and need for medical treatment. Idiographic analyses revealed that individuals used pain expression most frequently as a significant cue. Nomothetic analyses showed that higher pain expression VH and female VH were viewed as having higher pain intensity, higher pain unpleasantness, greater negative mood, worse coping, and a greater need to seek medical treatment than lower pain expression VH and male VH, respectively. Older VH were viewed as having worse coping and a greater need to seek medical treatment than younger VH. This innovative paradigm involving VH technology and a lens model design was shown to be highly effective and could serve as a model for future studies investigating pain-related decision making in healthcare providers.

  17. Compound lens

    DOEpatents

    Brixner, B.B.; Klein, M.M.; Winkler, M.A.

    1980-05-21

    The disclosure relates to at least one calcium fluoride optical element used in combination with at least two ordinary crown glass lens elements to greatly reduce secondary spectrum in optical systems.

  18. Compound lens

    DOEpatents

    Brixner, Berlyn B.; Klein, Morris M.; Winkler, Max A.

    1982-01-01

    The disclosure relates to at least one calcium fluoride optical element used in combination with at least two ordinary crown glass lens elements to greatly reduce secondary spectrum in optical systems.

  19. Barlow Lens

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    An additional lens that increases the effective focal length and magnification of a telescope. It is a negative diverging lens (either concave on both sides or, more usually, `plano-concave'—flat on one side and concave on the other) that is placed in the converging cone of light a short distance in front of the focal plane of the objective or primary mirror. By decreasing the angle at which the ...

  20. 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 ...

  1. Method of crosstalk reduction using lenticular lens

    NASA Astrophysics Data System (ADS)

    Lee, Hyoung; Lee, Kwang-Hoon; Kim, Sung-Kyu; Sohn, Kwang-Hoon

    2012-06-01

    Generally non-glass type three dimensional stereoscopic display systems should be considering human factor. Human factor include the crosstalk, motion parallax, types of display, lighting, age, unknown aspects around the human factors issues and user experience. Among these human factors, the crosstalk is very important human factor because; it reduces 3D effect and induces eye fatigue or dizziness. In these reason, we considered method of reduction crosstalk in three dimensional stereoscopic display systems. In this paper, we suggest method of reduction crosstalk using lenticular lens. Optical ray derived from projection optical system, converted to viewing zone shape by convolution of two apertures. In this condition, we can minimize and control the beam width by optical properties of lenticular lens (refractive, pitch, thickness, radius of curvature) and optical properties of projector (projection distance, optical features). In this processing, Gaussian distribution type shape is converted to rectangular distribution type shape. According to the beam width reduction will be reduce crosstalk, and it was verified used to lenticular lens.

  2. Accommodation dynamics in aging rhesus monkeys.

    PubMed

    Croft, M A; Kaufman, P L; Crawford, K S; Neider, M W; Glasser, A; Bito, L Z

    1998-12-01

    Accommodation, the mechanism by which the eye focuses on near objects, is lost with increasing age in humans and monkeys. This pathophysiology, called presbyopia, is poorly understood. We studied aging-related changes in the dynamics of accommodation in rhesus monkeys aged 4-24 yr after total iridectomy and midbrain implantation of an electrode to permit visualization and stimulation, respectively, of the eye's accommodative apparatus. Real-time video techniques were used to capture and quantify images of the ciliary body and lens. During accommodation in youth, ciliary body movement was biphasic, lens movement was monophasic, and both slowed as the structures approached their new steady-state positions. Disaccommodation occurred more rapidly for both ciliary body and lens, but with longer latent period, and slowed near the end point. With increasing age, the amplitude of lens and ciliary body movement during accommodation declined, as did their velocities. The latent period of lens and ciliary body movements increased, and ciliary body movement became monophasic. The latent period of lens and ciliary body movement during disaccommodation was not significantly correlated with age, but their velocity declined significantly. The age-dependent decline in amplitude and velocity of ciliary body movements during accommodation suggests that ciliary body dysfunction plays a role in presbyopia. The age changes in lens movement could be a consequence of increasing inelasticity or hardening of the lens, or of age changes in ciliary body motility.

  3. 21 CFR 886.1400 - Maddox lens.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Maddox lens. 886.1400 Section 886.1400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1400 Maddox lens. (a) Identification. A Maddox lens is a...

  4. 21 CFR 886.1400 - Maddox lens.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Maddox lens. 886.1400 Section 886.1400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1400 Maddox lens. (a) Identification. A Maddox lens is a...

  5. 21 CFR 886.1400 - Maddox lens.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Maddox lens. 886.1400 Section 886.1400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1400 Maddox lens. (a) Identification. A Maddox lens is a...

  6. 21 CFR 886.1400 - Maddox lens.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Maddox lens. 886.1400 Section 886.1400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1400 Maddox lens. (a) Identification. A Maddox lens is a...

  7. 21 CFR 886.1400 - Maddox lens.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Maddox lens. 886.1400 Section 886.1400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1400 Maddox lens. (a) Identification. A Maddox lens is a...

  8. Lens Status Influences the Association between CFH Polymorphisms and Age-Related Macular Degeneration: Findings from Two Population-Based Studies in Singapore

    PubMed Central

    Wong, Chee Wai; Liao, Jiemin; Cheung, Gemmy C.; Khor, Chiea Chuen; Vithana, Eranga N.; Wang, Jie Jin; Mitchell, Paul; Aung, Tin; Wong, Tien Y.; Cheng, Ching-Yu

    2015-01-01

    Aims To determine the differential effects of genetic polymorphism in CFH and ARMS2 on risk of age-related macular degeneration (AMD) between phakic vs. pseudophakic/aphakic eyes. Methods 9,529 eyes of 4,918 participants from the Singapore Malay Eye Study and Singapore Indian Eye Study were analyzed. Participants had detailed eye examinations, including slit-lamp examinations and dilated fundus photography. AMD grading was performed according to the Wisconsin age-related maculopathy grading system. Lens status was defined. Single nucleotide polymorphisms (SNPs) rs10801555 (Y402H) within CFH and rs3750847 in ARMS2 were assessed. The main outcome measure was early AMD or any AMD. Results No significant associations between the CFH Y402H genotypes and early AMD were found in phakic individuals. In contrast, among pseudophakic/aphakic individuals, the CFH Y402H risk genotypes were significantly associated with higher odds of early AMD, with an OR of 1.57 (95% CI: 1.07–2.29) for GA genotype and 2.40 (95% CI: 1.25–4.61) for AA genotype, compared to those with GG genotype. There was significant interaction between pseudophakic/aphakic status and CFH Y402H variant on risk of early AMD (p = 0.037), adjusting for age, gender, and the first 5 genetic principal components. No significant interaction was found between lens status and ARMS2 rs3750847. Conclusions CFH genetic polymorphism and pseudophakic/aphakic status may have a potential synergistic effect on early AMD, suggesting roles for the complement system and related pathways in the pathogenesis of AMD in eyes after cataract surgery. PMID:25786237

  9. Cadmium-induced induction of cell death in human lens epithelial cells: implications to smoking associated cataractogenesis.

    PubMed

    Kalariya, Nilesh M; Nair, Bindu; Kalariya, Denish K; Wills, Nancy K; van Kuijk, Frederik J G M

    2010-09-15

    Cadmium is reported to accumulate in human eye tissues suggesting its implication in diverse ocular pathology. Using an in vitro cell culture model we investigated the effects of cadmium on human lens epithelial cells (HLECs) (HLE-B3). We observed cadmium-induced dose- as well as time-dependent decline in HLECs viability which was exacerbated significantly upon reduction of intracellular glutathione levels by buthionine sulfoximine (BSO). There was a dose-dependent significant increase in lactate dehydrogenase (LDH) release from HLECs suggesting cadmium-induced alteration of membrane integrity as well as necrotic cell death. The decline in cell viability was also due to apoptosis of the HLECs as determined by quantifying % apoptotic cells as well as PARP cleavage. Moreover, release of apoptosis inducing factor (AIF) into the cytosol was also detected. Cadmium was also observed to increase oxidative stress, lipid peroxidation and activation of MAPK pathway in HLECs. Antioxidants like N-acetylcysteine (NAC) and alpha-Tocopherol significantly prevented cadmium-induced toxicity in HLECs. Our findings suggest that cadmium-induced elevated oxidative stress as well as activation of MAPK signaling cascade eventually led to cell death of HLECs through apoptosis as well as necrosis. The loss of HLECs by cadmium could possibly explain its implication in cataract development particularly associated with smoking.

  10. CCA 3101/4101 Environmental Humanities: The History of a Unit through an Ecopedagogical Lens

    ERIC Educational Resources Information Center

    Ryan, John Charles

    2012-01-01

    In 2011 the author taught, for the first time, the well-established unit CCA3101/4101 Environmental Humanities in the School of Communications and Arts at ECU (Edith Cowan University) in Western Australia. The unit has a 20-year history through associate professor Rod Giblett and parallels the development of the environmental humanities as a field…

  11. FDTD analysis of temperature elevation in the lens of human and rabbit models due to near-field and far-field exposures at 2.45 GHz.

    PubMed

    Oizumi, Takuya; Laakso, Ilkka; Hirata, Akimasa; Fujiwara, Osamu; Watanabe, Soichi; Taki, Masao; Kojima, Masami; Sasaki, Hiroshi; Sasaki, Kazuyuki

    2013-07-01

    The eye is said to be one of the most sensitive organs to microwave heating. According to previous studies, the possibility of microwave-induced cataract formation has been experimentally investigated in rabbit and monkey eyes, but not for the human eye due to ethical reasons. In the present study, the temperature elevation in the lens, the skin around the eye and the core temperature of numerical human and rabbit models for far-field and near-field exposures at 2.45 GHz are investigated. The temperature elevations in the human and rabbit models were compared with the threshold temperatures for inducing cataracts, thermal pain in the skin and reversible health effects such as heat exhaustion or heat stroke. For plane-wave exposure, the core temperature elevation is shown to be essential both in the human and in the rabbit models as suggested in the international guidelines and standards. For localised exposure of the human eye, the temperature elevation of the skin was essential, and the lens temperature did not reach its threshold for thermal pain. On the other hand, the lens temperature elevation was found to be dominant for the rabbit eye.

  12. 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

  13. Colour vision through intraocular lens.

    PubMed

    Mäntyjärvi, M; Syrjäkoski, J; Tuppurainen, K; Honkonen, V

    1997-04-01

    Fifty patients aged from 30 to 69 years (mean 54.7 +/- 11.3 years, SD) with a UV-protected monofocal polymethylmethacrylate intraocular lens (IOL) were examined with the Farnsworth-Munsell 100 hue (FM 100) test and the Color Vision Meter 712 anomaloscope. The spectral transmission of the same kind of IOLs as was used surgically was measured with Lambda 2 UV/VIS Spectrometer. In the FM 100 test, there was no significant difference between the results of the IOL eyes and normal eyes. However, the IOL eyes showed better error scores than the normal eyes in the blue-purple box IV in the FM 100 test. In the anomaloscope testing, the Rayleigh (red-green) equation showed no differences between the IOL patients and controls. In the Moreland (blue) equation, however, the mid matching point was significantly shifted towards more green (meaning better blue colour sensitivity) in the IOL eyes than in the control eyes. This is due to the spectral transmission of the IOLs which showed 80-90% transmission already starting at the wavelength of about 420 nm. In comparison, the transmission of the normal human lens reaches those percentages near 500 nm or even further at advanced age.

  14. Lens glutathione homeostasis: Discrepancies and gaps in knowledge standing in the way of novel therapeutic approaches.

    PubMed

    Fan, Xingjun; Monnier, Vincent M; Whitson, Jeremy

    2016-06-29

    Cataract is the major cause of blindness worldwide. The WHO has estimated around 20 million people have bilateral blindness from cataract, and that number is expected to reach 50 million in 2050. The cataract surgery is currently the main treatment approach, though often associated with complications, such as Posterior Capsule Opacification (PCO)-also known as secondary cataract. The lens is an avascular ocular structure equipped with an unusually high level of glutathione (GSH), which plays a vital role in maintaining lens transparency by regulating lenticular redox state. The lens epithelium and outer cortex are thought to be responsible for providing the majority of lens GSH via GSH de novo synthesis, assisted by a continuous supply of constituent amino acids from the aqueous humor, as well as extracellular GSH recycling from the gamma-glutamyl cycle. However, when de novo synthesis is impaired, in the presence of low GSH levels, as in the aging human lens, compensatory mechanisms exist, suggesting that the lens is able to uptake GSH from the surrounding ocular tissues. However, these uptake mechanisms, and the GSH source and its origin, are largely unknown. The lens nucleus does not have the ability to synthesize its own GSH and fully relies on transport from the outer cortex by yet unknown mechanisms. Understanding how aging reduces GSH levels, particularly in the lens nucleus, how it is associated with age-related nuclear cataract (ARNC), and how the lens compensates for GSH loss via external uptake should be a major research priority. The intent of this review, which is dedicated to the memory of David C. Beebe, is to summarize our current understanding of lens GSH homeostasis and highlight discrepancies and gaps in knowledge that stand in the way of pharmacologically minimizing the impact of declining GSH content in the prevention of age-related cataract.

  15. Growth of the eye lens: I. Weight accumulation in multiple species

    PubMed Central

    2014-01-01

    Purpose To examine the accumulation of wet and/or dry weight in the ocular lens as a function of age in different species. Methods Wet weights and/or fixed dry weights were obtained from measurements in the author’s laboratory and from the literature for over 14,000 lenses of known-ages, representing 130 different species. Various algorithms were tested to determine the most suitable for describing the relationship between lens weight and age. Results For 126 of the species examined, lens growth is continuous throughout life but asymptotic and can be reasonably described with a single logistic equation, W=Wm e-(k/A), where W is lens wet or dry weight; Wm is the maximum asymptotic weight, k is the logistic growth constant and A is the time from conception. For humans, elephants, hippopotami, minks, wild goats and woodchucks, lens growth appears to be biphasic. No gender differences could be detected in the lens weights for 70 species but male lenses are reportedly 10% larger than those of females in northern fur seals and pheasants. Dry weight accumulation is faster than that for wet weight in all species except birds and reptiles where the rates are the same. Low lens growth rates are associated with small animals with short gestation periods and short life spans. Conclusions Lens growth is continuous throughout life and, for most species, is independent of gender. For most, growth takes place through a monophasic asymptotic mode and is unaffected by events such as hibernation. This makes lens weight measurement a reliable tool for age determination of species culled in the wild. Compaction of the growing lens generates different properties, appropriate to an animal's lifestyle. How these events are controlled remains to be established. PMID:24715758

  16. 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.

  17. 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

  18. 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…

  19. Reactive Oxygen Species and the Aging Eye: Specific Role of Metabolically Active Mitochondria in Maintaining Lens Function and in the Initiation of the Oxidation-Induced Maturity Onset Cataract--A Novel Platform of Mitochondria-Targeted Antioxidants With Broad Therapeutic Potential for Redox Regulation and Detoxification of Oxidants in Eye Diseases.

    PubMed

    Babizhayev, Mark A; Yegorov, Yegor E

    2016-01-01

    The aging eye appears to be at considerable risk from oxidative stress. A great deal of research indicates that dysfunctional mitochondria are the primary site of reactive oxygen species (ROS). More than 95% of O2 produced during normal metabolism is generated by the electron transport chain in the inner mitochondrial membrane. Mitochondria are also the major target of ROS. Cataract formation, the opacification of the eye lens, is one of the leading causes of human blindness worldwide, accounting for 47.8% of all causes of blindness. Cataracts result from the deposition of aggregated proteins in the eye lens and lens fiber cell plasma membrane damage, which causes clouding of the lens, light scattering, and obstruction of vision. ROS-induced damage in the lens cell may consist of oxidation of proteins, DNA damage, and/or lipid peroxidation, all of which have been implicated in cataractogenesis. This article is an attempt to integrate how mitochondrial ROS are altered in the aging eye along with those protective and repair therapeutic systems believed to regulate ROS levels in ocular tissues and how damage to these systems contributes to age-onset eye disease and cataract formation. Mitochondria-targeted antioxidants might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner mitochondrial membrane in vivo. As a result of the combination of weak metal chelating, OH and lipid peroxyl radicals scavenging, reducing activities to liberated fatty acid, and phospholipid hydroperoxides, carnosine and carcinine appear to be physiological antioxidants able to efficiently protect the lipid phase of biologic membranes and aqueous environments and act as the antiapoptotic natural drug compounds The authors developed and patented the new ophthalmic compositions, including N-acetylcarnosine, acting as a prodrug of naturally targeted to mitochondria L-carnosine endowed with pluripotent antioxidant activities combined with mitochondria

  20. Acetyl-l-carnitine prevents homocysteine-induced suppression of Nrf2/Keap1 mediated antioxidation in human lens epithelial cells.

    PubMed

    Yang, Shui-Ping; Yang, Xiu-Zhen; Cao, Guo-Ping

    2015-07-01

    Previous studies have revealed that high levels of serum homocysteine (Hcy) are closely associated with the development of juvenile and age-related cataracts. An increased concentration of Hcy is likely to induce gene specific demethylation in DNA promoter regions. The aim of the present study was to prevent this demethylation by administering acetyl-l-carnitine (ALCAR) to human lens epithelial cells (HLECs). Different concentrations of Hcy were used to treat HLECs for 3, 6, 12 and 24 h and the findings were used to determine the optimum dose to induce endoplasmic reticulum (ER) stress. Similarly, the concentration of ALCAR was standardized. The production of reactive oxygen species (ROS) and the percentage of cells undergoing cell death were measured. The levels of antioxidants, ER stress-associated proteins, mRNA levels of nuclear factor erythroid-2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1) and promoter DNA methylation of the Keap1 gene were also assessed. Hcy was observed to induce ER stress, produce ROS and lead to cell death. However, administration of ALCAR prevented these effects to a significant degree. Additionally, western blot analysis revealed that ALCAR increased the levels of antioxidant proteins, including catalase, superoxide dismutase, glutathione peroxidase, Nrf2, Keap1 and glutathione. Similarly, the reverse transcription-quantitative polymerase chain reaction experiments on Nrf2 and Keap1, as well as the bisulfite genomic DNA sequencing analysis revealed a preventive effect of ALCAR against Hcy-induced ER stress. The ER stress-induced activation of the unfolded protein response is responsible for demethylation of Keap1 promoter DNA to activate the expression of the Keap1 protein, which then increases the targeting of Nrf2 for proteosomal degradation. This decrease in Nrf2 activity represses the transcription of numerous antioxidant enzyme genes and alters the redox-balance towards lens oxidation. However, treatment

  1. SiRNA Targeting mTOR Effectively Prevents the Proliferation and Migration of Human Lens Epithelial Cells

    PubMed Central

    Zhang, Chunmei; Liu, Jingjing; Jin, Na; Zhang, Guiming; Xi, Yahui; Liu, Hongling

    2016-01-01

    Posterior capsule opacification (PCO) is the most common complication that causes visual decrease after extracapsular cataract surgery. The primary cause of PCO formation is the proliferation of the residual lens epithelial cells (LECs). The mammalian target of rapamycin (mTOR) plays an important role in the growth and migration of LECs. In the current study, we used small interfering RNA (siRNA) to specifically attenuate mTOR in human lens epithelial B3 cells (HLE B3). We aimed to examine the effect of mTOR-siRNA on the proliferation, migration and epithelial-to-mesenchymal transition (EMT) of HLE B3 cells and explore the underlying mechanisms. The mTOR-siRNA was transfected into HLE B3 cells using lipofectamine 2000. The mRNA and protein levels of mTOR were examined to confirm the efficiency of mTOR-siRNA. The levels of mRNA and protein as well as the activity of mTOR down-stream effectors p70 ribosomal protein S6 kinase (p70S6K) and protein kinase B (PKB, AKT) were examined using real-time PCR or Western blot, respectively. The cell proliferation was determined using cell counting kit (CCK) 8 and cell growth curve assay. The cell migration was examined using Transwell system and Scratch assay. MTOR-siRNA effectively eliminated mTOR mRNA and protein. The proliferation and migration were significantly suppressed by mTOR-siRNA transfection. mTOR-siRNA reduced the mRNA of p70S6K and AKT in a time-dependent manner. Furthermore, the phosphorylation of p70S6K and AKT was decreased by mTOR-siRNA. MTOR-siRNA also eliminated the formation of mTORC1 and mTORC2 protein complex and blocked the transforming growth factor (TGF)-β-induced EMT. Our results suggested that mTOR-siRNA could effectively inhibit the proliferation, migration and EMT of HLE B3 cells through the inhibition of p70S6K and AKT. These results indicated that mTOR-siRNA might be an effective agent inhibiting HLE cells growth and EMT following cataract surgery and provide an alternative therapy for preventing

  2. Histological evaluation of coagulation foci produced in the human lens with a holmium laser

    NASA Astrophysics Data System (ADS)

    Kecik, Dariusz; Kecik, Tadeusz; Pratnicki, Antoni; Kasprzak, Jan; Kecik, Mariusz

    1997-10-01

    We present the results of histological evaluation of human lenses treated with the holmium laser. The lenses, extracted at the time of extracapsular surgery for cataract, were placed in containers filled with Ringer's solution. After treatment with laser-emitted radiation they were histologically evaluated. The formation of crater-like defects was found in the material studied.

  3. 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

  4. Lens Biodiversity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Lens genus includes the cultivated L. culinaris, and wild subspecies orientalis - the progenitor, tomentosus, and odemensis, are in the primary genepool, while L. ervoides, L. nigricans and L. lamottei are in the secondary – tertiary gene pool. The Middle East is the primary centre of diversity ...

  5. Sprouty2 Suppresses Epithelial-Mesenchymal Transition of Human Lens Epithelial Cells through Blockade of Smad2 and ERK1/2 Pathways

    PubMed Central

    Chen, Chuan; Chen, Xiaoyun; Qin, Yingyan; Qu, Bo; Luo, Lixia; Lin, Haotian; Wu, Mingxing; Chen, Weirong; Liu, Yizhi

    2016-01-01

    Transforming growth factor β (TGFβ)-induced epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) plays a key role in the pathogenesis of anterior subcapsular cataract (ASC) and capsule opacification. In mouse lens, Sprouty2 (Spry2) has a negative regulatory role on TGFβ signaling. However, the regulation of Spry2 during ASC development and how Spry2 modulates TGFβ signaling pathway in human LECs have not been characterized. Here, we demonstrate that Spry2 expression level is decreased in anterior capsule LECs of ASC patients. Spry2 negatively regulates TGFβ2-induced EMT and migration of LECs through inhibition of Smad2 and ERK1/2 phosphorylation. Also, blockade of Smad2 or ERK1/2 activation suppresses EMT caused by Spry2 downregulation. Collectively, our results for the first time show in human LECs that Spry2 has an inhibitory role in TGFβ signaling pathway. Our findings in human lens tissue and epithelial cells suggest that Spry2 may become a novel therapeutic target for the prevention and treatment of ASC and capsule opacification. PMID:27415760

  6. 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

  7. A Class I UV-Blocking (senofilcon A) Soft Contact Lens Prevents UVA-induced Yellow Fluorescence and NADH loss in the Rabbit Lens Nucleus in vivo

    PubMed Central

    Giblin, Frank J.; Lin, Li-Ren; Simpanya, Mukoma F.; Leverenz, Victor R.; Fick, Catherine E.

    2012-01-01

    It is known that fluorescence, much of it caused by UVA light excitation, increases in the aging human lens, resulting in loss of sharp vision. This study used an in vivo animal model to investigate UVA-excited fluorescence in the rabbit lens, which contains a high level of the UVA chromophore NADH, existing both free and bound to λ-crystallin. Also, the ability of a Class I (senofilcon A) soft contact lens to protect against UVA-induced effects on the rabbit lens was tested. Rabbit eyes were irradiated with UVA light in vivo (100 mW/cm2 on the cornea) for 1 hour using monochromatic 365 nm light. Irradiation was conducted in the presence of either a senofilcon A contact lens, a minimally UV-absorbing lotrafilcon A contact lens, or no contact lens at all. Eyes irradiated without a contact lens showed blue 365 nm-excited fluorescence initially, but this changed to intense yellow fluorescence after 1 hour. Isolated, previously irradiated lenses exhibited yellow fluorescence originating from the lens nucleus when viewed under 365 nm light, but showed normal blue fluorescence arising from the cortex. Previously irradiated lenses also exhibited a faint yellow color when observed under visible light. The senofilcon A contact lens protected completely against the UVA-induced effects on fluorescence and lens yellowing, whereas the lotrafilcon A lens showed no protection. The UVA-exposure also produced a 53% loss of total NADH (free plus bound) in the lens nucleus, with only a 13% drop in the anterior cortex. NADH loss in the nucleus was completely prevented with use of a senofilcon A contact lens, but no significant protection was observed with a lotrafilcon A lens. Overall, the senofilcon A lens provided an average of 67% protection against UVA-induced loss of four pyridine nucleotides in four different regions of the lens. HPLC analysis with fluorescence detection indicated a nearly six-fold increase in 365 nm-excited yellow fluorescence arising from lens nuclear

  8. Analysis of newspaper coverage of active aging through the lens of the 2002 World Health Organization Active Ageing Report: A Policy Framework and the 2010 Toronto Charter for Physical Activity: A Global Call for Action.

    PubMed

    Abdullah, Boushra; Wolbring, Gregor

    2013-12-05

    As populations continue to grow older, efforts to support the process of aging well are important goals. Various synonyms are used to cover aging well, such as active aging. The World Health Organization published in 2002 the report Active Ageing: A Policy Framework that according to the call for papers, has brought active ageing to the forefront of international public health awareness. The 2010 Toronto Charter for Physical Activity: A Global Call for Action was singled out in the call for papers as a key document promoting physical activity one goal of the 2002 WHO active aging policy framework. Media are to report to the public topics of importance to them. We investigated the newspaper coverage of aging well and synonymous terms such as active aging through the lens of the 2002 WHO active aging policy framework and the 2010 Toronto Charter for Physical Activity. As sources we used the following newspapers: China Daily, The Star (Malaysia), two UK newspapers (The Guardian, The Times), a database of 300 Canadian newspapers (Canadian Newsstand) and a US newspaper (The New York Times). The study generated data answering the following four research questions: (1) how often are the 2002 WHO active aging policy framework and the 2010 Toronto Charter for Physical Activity mentioned; (2) how often is the topic of active aging and terms conveying similar content (aging well, healthy aging, natural aging and successful aging) discussed; (3) which of the issues flagged as important in the 2002 WHO active aging policy framework and the 2010 Toronto Charter for Physical Activity are covered in the newspaper coverage of active aging and synonymous terms; (4) which social groups were mentioned in the newspapers covered. The study found a total absence of mentioning of the two key documents and a low level of coverage of "active aging" and terms conveying similar content. It found further a lack of engagement with the issues raised in the two key documents and a low level of

  9. Looking at the ICF and human communication through the lens of classification theory.

    PubMed

    Walsh, Regina

    2011-08-01

    This paper explores the insights that classification theory can provide about the application of the International Classification of Functioning, Disability and Health (ICF) to communication. It first considers the relationship between conceptual models and classification systems, highlighting that classification systems in speech-language pathology (SLP) have not historically been based on conceptual models of human communication. It then overviews the key concepts and criteria of classification theory. Applying classification theory to the ICF and communication raises a number of issues, some previously highlighted through clinical application. Six focus questions from classification theory are used to explore these issues, and to propose the creation of an ICF-related conceptual model of communicating for the field of communication disability, which would address some of the issues raised. Developing a conceptual model of communication for SLP purposes closely articulated with the ICF would foster productive intra-professional discourse, while at the same time allow the profession to continue to use the ICF for purposes in inter-disciplinary discourse. The paper concludes by suggesting the insights of classification theory can assist professionals to apply the ICF to communication with the necessary rigour, and to work further in developing a conceptual model of human communication.

  10. The Deepwater Horizon Oil Spill Through the Lens of Human Health and the Ecosystem.

    PubMed

    Lichtveld, Maureen; Sherchan, Samendra; Gam, Kaitlyn B; Kwok, Richard K; Mundorf, Christopher; Shankar, Arti; Soares, Lissa

    2016-12-01

    This review examines current research ascertaining the impact of the Deepwater Horizon oil spill on human health and ecosystems. Driven by the need to strategically focus research funding, the authors also assess the implications of those findings and promote a transdisciplinary research agenda addressing critical gaps.Epidemiologic studies conducted in workers and vulnerable communities in the spill's aftermath showed that non-chemical stressors affect resilience. Ecosystem-wise salt marsh species showed variability in structural and functional changes, attributed to species-specific tolerance, oil exposure, and belowground plant organs damage.Lacking baseline exposure assessment data hampers assessing the impact of chemical stressors. Research priorities include leveraging existing women/child dyads and worker cohorts to advance exposure characterization and counter early adverse effects in most vulnerable populations. Key policy gaps include mandated just-in-time emergency resources to ascertain immediate post-event exposures and contemporary legislation addressing human and ecosystem health in an integrated rather than silo fashion.

  11. 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)

  12. 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

  13. Analysis of Newspaper Coverage of Active Aging through the Lens of the 2002 World Health Organization Active Ageing Report: A Policy Framework and the 2010 Toronto Charter for Physical Activity: A Global Call for Action

    PubMed Central

    Abdullah, Boushra; Wolbring, Gregor

    2013-01-01

    As populations continue to grow older, efforts to support the process of aging well are important goals. Various synonyms are used to cover aging well, such as active aging. The World Health Organization published in 2002 the report Active Ageing: A Policy Framework that according to the call for papers, has brought active ageing to the forefront of international public health awareness. The 2010 Toronto Charter for Physical Activity: A Global Call for Action was singled out in the call for papers as a key document promoting physical activity one goal of the 2002 WHO active aging policy framework. Media are to report to the public topics of importance to them. We investigated the newspaper coverage of aging well and synonymous terms such as active aging through the lens of the 2002 WHO active aging policy framework and the 2010 Toronto Charter for Physical Activity. As sources we used the following newspapers: China Daily, The Star (Malaysia), two UK newspapers (The Guardian, The Times), a database of 300 Canadian newspapers (Canadian Newsstand) and a US newspaper (The New York Times). The study generated data answering the following four research questions: (1) how often are the 2002 WHO active aging policy framework and the 2010 Toronto Charter for Physical Activity mentioned; (2) how often is the topic of active aging and terms conveying similar content (aging well, healthy aging, natural aging and successful aging) discussed; (3) which of the issues flagged as important in the 2002 WHO active aging policy framework and the 2010 Toronto Charter for Physical Activity are covered in the newspaper coverage of active aging and synonymous terms; (4) which social groups were mentioned in the newspapers covered. The study found a total absence of mentioning of the two key documents and a low level of coverage of “active aging” and terms conveying similar content. It found further a lack of engagement with the issues raised in the two key documents and a low level

  14. Fluidic adaptive lens of transformable lens type

    NASA Astrophysics Data System (ADS)

    Zhang, De-Ying; Justis, Nicole; Lo, Yu-Hwa

    2004-05-01

    Fluidic adaptive lenses with a transformable lens type were demonstrated. By adjusting the fluidic pressure, not only can the lens properties, such as the focal distance and numerical aperture, be tuned dynamically but also different lens types, such as planoconvex, planoconcave, biconvex, biconcave, positive meniscus, and negative meniscus lenses, can be formed. The shortest focal length for a 20 mm aperture adaptive lens is 14.3 mm when the device is transformed into a positive lens, and -6.3 mm when transformed into a negative lens. The maximum resolution of the fluidic lens is better than 40 line pairs/mm.

  15. 2-ammonio-6-(3-oxidopyridinium-1-yl)hexanoate (OP-lysine) is a newly identified advanced glycation end product in cataractous and aged human lenses.

    PubMed

    Argirov, Ognyan K; Lin, Bin; Ortwerth, Beryl J

    2004-02-20

    Post-translational modifications of proteins take place during the aging of human lens. The present study describes a newly isolated glycation product of lysine, which was found in the human lens. Cataractous and aged human lenses were hydrolyzed and fractionated using reverse-phase and ion-exchange high performance liquid chromatography (HPLC). One of the nonproteinogenic amino acid components of the hydrolysates was identified as a 3-hydroxypyridinium derivative of lysine, 2-ammonio-6-(3-oxidopyridinium-1-yl)hexanoate (OP-lysine). The compound was synthesized independently from 3-hydroxypyridine and methyl 2-[(tert-butoxycarbonyl)amino]-6-iodohexanoate. The spectral and chromatographic properties of the synthetic OP-lysine and the substance isolated from hydrolyzed lenses were identical. HPLC analysis showed that the amounts of OP-lysine were higher in water-insoluble compared with water-soluble proteins and was higher in a pool of cataractous lenses compared with normal aged lenses, reaching 500 pmol/mg protein. The model incubations showed that an anaerobic reaction mixture of Nalpha-tert-butoxycarbonyllysine, glycolaldehyde, and glyceraldehyde could produce the Nalpha-t-butoxycarbonyl derivative of OP-lysine. The irradiation of OP-lysine with UVA under anaerobic conditions in the presence of ascorbate led to a photochemical bleaching of this compound. Our results argue that OP-lysine is a newly identified glycation product of lysine in the lens. It is a marker of aging and pathology of the lens, and its formation could be considered as a potential cataract risk-factor based on its concentration and its photochemical properties.

  16. 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.

  17. 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

  18. Electromagnetic noise inhibits radiofrequency radiation-induced DNA damage and reactive oxygen species increase in human lens epithelial cells

    PubMed Central

    Wu, Wei; Wang, KaiJun; Ni, Shuang; Ye, PanPan; Yu, YiBo; Ye, Juan; Sun, LiXia

    2008-01-01

    Purpose The goal of this study was to investigate whether superposing of electromagnetic noise could block or attenuate DNA damage and intracellular reactive oxygen species (ROS) increase of cultured human lens epithelial cells (HLECs) induced by acute exposure to 1.8 GHz radiofrequency field (RF) of the Global System for Mobile Communications (GSM). Methods An sXc-1800 RF exposure system was used to produce a GSM signal at 1.8 GHz (217 Hz amplitude-modulated) with the specific absorption rate (SAR) of 1, 2, 3, and 4 W/kg. After 2 h of intermittent exposure, the ROS level was assessed by the fluorescent probe, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). DNA damage to HLECs was examined by alkaline comet assay and the phosphorylated form of histone variant H2AX (γH2AX) foci formation assay. Results After exposure to 1.8 GHz RF for 2 h, HLECs exhibited significant intracellular ROS increase in the 2, 3, and 4 W/kg groups. RF radiation at the SAR of 3 W/kg and 4 W/kg could induce significant DNA damage, examined by alkaline comet assay, which was used to detect mainly single strand breaks (SSBs), while no statistical difference in double strand breaks (DSBs), evaluated by γH2AX foci, was found between RF exposure (SAR: 3 and 4 W/kg) and sham exposure groups. When RF was superposed with 2 μT electromagnetic noise could block RF-induced ROS increase and DNA damage. Conclusions DNA damage induced by 1.8 GHz radiofrequency field for 2 h, which was mainly SSBs, may be associated with the increased ROS production. Electromagnetic noise could block RF-induced ROS formation and DNA damage. PMID:18509546

  19. Study of Oxidative Stress in Human Lens Epithelial Cells Exposed to 1.8 GHz Radiofrequency Fields

    PubMed Central

    Ni, Shuang; Yu, Yibo; Zhang, Yidong; Wu, Wei; Lai, Kairan; Yao, Ke

    2013-01-01

    Objectives The aims of the present study were to determine oxidative stress and to explore possible reasons of reactive oxygen species (ROS) increase in human lens epithelial (HLE) B3 cells exposed to low intensity 1.8 GHz radiofrequency fields (RF). Methods The HLE B3 cells were divided into RF exposure and RF sham-exposure groups. The RF exposure intensity was at specific absorption rate (SAR) of 2, 3, or 4 W/kg. The ROS levels were measured by a fluorescent probe 2′7′-dichlorofluorescin diacetate (DCFH-DA) assay in the HLE B3 cells exposed to 1.8 GHz RF for 0.5, 1, and 1.5 h. Lipid peroxidation and cellular viability were detected by an MDA test and Cell Counting Kit-8 (CCK-8) assays, respectively, in the HLE B3 cells exposed to 1.8 GHz RF for 6, 12, and 24 h, respectively. The mRNA expression of SOD1, SOD2, CAT, and GPx1 genes and the expression of SOD1, SOD2, CAT, and GPx1 proteins was measured by qRT-PCR and Western blot assays in the HLE B3 cells exposed to 1.8 GHz RF for 1 h. Results The ROS and MDA levels significantly increased (P<0.05) in the RF exposure group and that the cellular viability, mRNA expression of four genes, and expression of four proteins significantly decreased (P<0.05) compared with the RF sham-exposure group. Conclusions Oxidative stress is present in HLE B3 cells exposed to 1.8 GHz low-intensity RF and that the increased production of ROS may be related to down-regulation of four antioxidant enzyme genes induced by RF exposure. PMID:23991100

  20. Thermal Lens Microscope

    NASA Astrophysics Data System (ADS)

    Uchiyama, Kenji; Hibara, Akihide; Kimura, Hiroko; Sawada, Tsuguo; Kitamori, Takehiko

    2000-09-01

    We developed a novel laser microscope based on the thermal lens effect induced by a coaxial beam comprised of excitation and probe beams. The signal generation mechanism was confirmed to be an authentic thermal lens effect from the measurement of signal and phase dependences on optical configurations between the sample and the probe beam focus, and therefore, the thermal lens effect theory could be applied. Two-point spatial resolution was determined by the spot size of the excitation beam, not by the thermal diffusion length. Sensitivity was quite high, and the detection ability, evaluated using a submicron microparticle containing dye molecules, was 0.8 zmol/μm2, hence a distribution image of trace chemical species could be obtained quantitatively. In addition, analytes are not restricted to fluorescent species, therefore, the thermal lens microscope is a promising analytical microscope. A two-dimensional image of a histamine molecule distribution, which was produced in mast cells at the femtomole level in a human nasal mucous polyp, was obtained.

  1. Wearable telescopic contact lens.

    PubMed

    Arianpour, Ashkan; Schuster, Glenn M; Tremblay, Eric J; Stamenov, Igor; Groisman, Alex; Legerton, Jerry; Meyers, William; Amigo, Goretty Alonso; Ford, Joseph E

    2015-08-20

    We describe the design, fabrication, and testing of a 1.6 mm thick scleral contact lens providing both 1× and 2.8× magnified vision paths, intended for use as a switchable eye-borne telescopic low-vision aid. The F/9.7 telescopic vision path uses an 8.2 mm diameter annular entrance pupil and 4 internal reflections in a polymethyl methacrylate precision optic. This gas-impermeable insert is contained inside a smooth outer casing of rigid gas-permeable polymer, which also provides achromatic correction for refraction at the curved lens face. The unmagnified F/4.1 vision path is through the central aperture of the lens, with additional transmission between the annular telescope rings to enable peripheral vision. We discuss potential solutions for providing oxygenation for an extended wear version of the lens. The prototype lenses were characterized using a scale-model human eye, and telescope functionality was confirmed in a small-scale clinical (nondispensed) demonstration.

  2. 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…

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. Involvement of MsrB1 in the regulation of redox balance and inhibition of peroxynitrite-induced apoptosis in human lens epithelial cells.

    PubMed

    Jia, Yi; Li, Yi; Du, Shaoqing; Huang, Kaixun

    2012-07-01

    Methionine sulfoxide reductases (Msrs) in lens cells are important for the maintenance of lens cell viability and resistance to oxidative stress damage. Peroxynitrite (ONOO(-)), as a strong oxidizing and nitrating agent, occurred in diabetic retinopathy patients and diabetic model animal. In an attempt to shed light on the roles of MsrB1, known as selenoprotein R, in protecting human lens epithelial (HLE) cells against peroxynitrite damage, and contribution of loss of its normal activity to cataract, the influences of MsrB1 gene silencing on peroxynitrite-induced apoptosis in HLE cells were studied. The results showed that both exogenous peroxynitrite and MsrB1 gene silencing by short interfering RNA (siRNA) independently resulted in oxidative stress, endoplasmic reticulum (ER) stress, activation of caspase-3 as well as an increase of apoptosis in HLE cells; moreover, when MsrB1-gene-silenced cells were exposed to 300 μM peroxynitrite, these indexes were further aggravated at the same conditions and DNA strand breaks occurred. The results demonstrate that in HLE cells MsrB1 may play important roles in regulating redox balance and mitigating ER stress as induced by oxidative stress under physiological conditions; MsrB1 may also protect HLE cells against peroxynitrite-induced apoptosis by inhibiting the activation of caspase-3 and oxidative damage of DNA under pathological conditions. Our results imply that loss of its normal activity is likely to contribute to cataract.

  10. Crystalline lens MTF measurement during simulated accommodation

    NASA Astrophysics Data System (ADS)

    Borja, David; Takeuchi, Gaku; Ziebarth, Noel; Acosta, Ana C.; Manns, Fabrice; Parel, Jean-Marie

    2005-04-01

    Purpose: To design and test an optical system to measure the optical quality of post mortem lenses during simulated accommodation. Methods: An optical bench top system was designed to measure the point spread function and calculate the modulation transfer function (MTF) of monkey and human ex-vivo crystalline lenses. The system consists of a super luminescent diode emitting at 850nm, collimated into a 3mm beam which is focused by the ex-vivo lens under test. The intensity distribution at the focus (point spread function) is re-imaged and magnified onto a beam profiler CCD camera. The optical quality in terms of spatial frequency response (modulation transfer function) is calculated by Fourier transform of the point spread function. The system was used on ex-vivo lenses with attached zonules, ciliary body and sclera. The sclera was glued to 8 separate PMMA segments and stretched radial by 5mm on an accommodation simulating lens stretching device. The point spread function was measured for each lens in the relaxed and stretched state for 5 human (ages 38-86 years) and 5 cynomolgus monkey (ages 53 - 67 months) fresh post mortem crystalline lenses. Results: Stretching induced measurable changes in the MTF. The cutoff frequency increased from 54.4+/-13.6 lp/mm unstretched to 59.5+/-21.4 lp/mm stretched in the post-presbyopic human and from 51.9+/-24.7 lp/mm unstretched to 57.7+/-18.5 lp/mm stretched cynomolgus monkey lenses. Conclusion: The results demonstrate the feasibility of measuring the optical quality of ex-vivo human and cynomolgus monkey lenses during simulated accommodation. Additional experiments are underway to quantify changes in optical quality induced by stretching.

  11. [In vivo measurement of the distribution of the refractive index of the human lens using a Scheimpflug photo of the anterior eye segment and a helium-neon laser beam].

    PubMed

    Roth, E H; Kluxen, G

    1990-01-01

    The distribution of the refractive index of the human lens in vivo is measured by taking a Scheimpflug photograph of the anterior segment while simultaneously passing a HeNe laser beam through these structures. The refractive index can be evaluated simply by using the Snellens formula for refraction on the course of the beam after reevaluating the Scheimpflug photograph for distortion. It is possible to perform this measurement during accommodation and in the relaxed lens.

  12. Collection Mode Lens System

    DOEpatents

    Fletcher, Daniel A.; Kino, Gordon S.

    2002-11-05

    A lens system including a collection lens and a microlens spaced from the collection lens adjacent the region to be observed. The diameter of the observablel region depends substantially on the radius of the microlens.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. Age-related changes in the kinetics of human lenses: prevention of the cataract

    PubMed Central

    Pescosolido, Nicola; Barbato, Andrea; Giannotti, Rossella; Komaiha, Chiara; Lenarduzzi, Fiammetta

    2016-01-01

    The crystalline lens is a transparent, biconvex structure in the eye that, along with the cornea, helps to refract light to be focused on the retina and, by changing shape, it adjusts focal distance (accommodation). The three classes of structural proteins found in the lens are α, β, and γ crystallins. These proteins make up more than 90% of the total dry mass of the eye lens. Other components which can be found are sugars, lipids, water, several antioxidants and low weight molecules. When ageing changes occur in the lens, it causes a gradual reduction in transparency, presbyopia and an increase in the scattering and aberration of light waves as well as a degradation of the optical quality of the eye. The main changes that occur with aging are: 1) reduced diffusion of water from the outside to the inside of the lens and from its cortical to its nuclear zone; 2) crystalline change due to the accumulation of high molecular weight aggregates and insoluble proteins; 3) production of advanced glycation end products (AGEs), lipid accumulation, reduction of reduced glutathione content and destruction of ascorbic acid. Even if effective strategies in preventing cataract onset are not already known, good results have been reached in some cases with oral administration of antioxidant substances such as caffeine, pyruvic acid, epigallocatechin gallate (EGCG), α-lipoic acid and ascorbic acid. Furthermore, methionine sulfoxide reductase A (MSRA) over expression could protect lens cells both in presence and in absence of oxidative stress-induced damage. Nevertheless, promising results have been obtained by reducing ultraviolet-induced oxidative damage. PMID:27803872

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Optical density of the crystalline lens

    SciTech Connect

    Hemenger, R.P.

    1982-01-01

    The optical density for the noncataractous crystalline lens is written as a sum of two terms, each with a specific dependence on wavelength. The first term, proportional to 1/lambda 2, represents all light-scattering processes in the lens. The second term, assumed significant only for lambda less than or equal to 500 nm, accounts for absorption by lens pigments. By analyzing transmittance data on lenses of subjects aged 21 to 63 years, a spectrum for light absorption by lens pigment is derived and it is shown to be essentially the same for all of the lenses.

  5. 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.

  6. 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

  7. Atomic force microscopy and Langmuir–Blodgett monolayer technique to assess contact lens deposits and human meibum extracts☆

    PubMed Central

    Hagedorn, Sarah; Drolle, Elizabeth; Lorentz, Holly; Srinivasan, Sruthi; Leonenko, Zoya; Jones, Lyndon

    2015-01-01

    Purpose The purpose of this exploratory study was to investigate the differences in meibomian gland secretions, contact lens (CL) lipid extracts, and CL surface topography between participants with and without meibomian gland dysfunction (MGD). Methods Meibum study: Meibum was collected from all participants and studied via Langmuir–Blodgett (LB) deposition with subsequent Atomic Force Microscopy (AFM) visualization and surface roughness analysis. CL Study: Participants with and without MGD wore both etafilcon A and balafilcon A CLs in two different phases. CL lipid deposits were extracted and analyzed using pressure-area isotherms with the LB trough and CL surface topographies and roughness values were visualized using AFM. Results Meibum study: Non-MGD participant meibum samples showed larger, circular aggregates with lower surface roughness, whereas meibum samples from participants with MGD showed more lipid aggregates, greater size variability and higher surface roughness. CL Study: Worn CLs from participants with MGD had a few large tear film deposits with lower surface roughness, whereas non-MGD participant-worn lenses had many small lens deposits with higher surface roughness. Balafilcon A pore depths were shallower in MGD participant worn lenses when compared to non-MGD participant lenses. Isotherms of CL lipid extracts from MGD and non-MGD participants showed a seamless rise in surface pressure as area decreased; however, extracts from the two different lens materials produced different isotherms. Conclusions MGD and non-MGD participant-worn CL deposition were found to differ in type, amount, and pattern of lens deposits. Lipids from MGD participants deposited irregularly whereas lipids from non-MGD participants showed more uniformity. PMID:25620317

  8. 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.

  9. 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.

  10. 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.

  11. Selenoprotein R Protects Human Lens Epithelial Cells against D-Galactose-Induced Apoptosis by Regulating Oxidative Stress and Endoplasmic Reticulum Stress.

    PubMed

    Dai, Jie; Liu, Hongmei; Zhou, Jun; Huang, Kaixun

    2016-02-10

    Selenium is an essential micronutrient for humans. Much of selenium's beneficial influence on health is attributed to its presence within 25 selenoproteins. Selenoprotein R (SelR), known as methionine sulfoxide reductase B1 (MsrB1), is a selenium-dependent enzyme that, like other Msrs, is required for lens cell viability. In order to investigate the roles of SelR in protecting human lens epithelial (hLE) cells against damage, the influences of SelR gene knockdown on d-galactose-induced apoptosis in hLE cells were studied. The results showed that both d-galactose and SelR gene knockdown by siRNA independently induced oxidative stress. When SelR-gene-silenced hLE cells were exposed to d-galactose, glucose-regulated protein 78 (GRP78) protein level was further increased, mitochondrial membrane potential was significantly decreased and accompanied by a release of mitochondrial cytochrome c. At the same time, the apoptosis cells percentage and the caspase-3 activity were visibly elevated in hLE cells. These results suggested that SelR might protect hLE cell mitochondria and mitigating apoptosis in hLE cells against oxidative stress and endoplasmic reticulum (ER) stress induced by d-galactose, implying that selenium as a micronutrient may play important roles in hLE cells.

  12. Selenoprotein R Protects Human Lens Epithelial Cells against d-Galactose-Induced Apoptosis by Regulating Oxidative Stress and Endoplasmic Reticulum Stress

    PubMed Central

    Dai, Jie; Liu, Hongmei; Zhou, Jun; Huang, Kaixun

    2016-01-01

    Selenium is an essential micronutrient for humans. Much of selenium’s beneficial influence on health is attributed to its presence within 25 selenoproteins. Selenoprotein R (SelR), known as methionine sulfoxide reductase B1 (MsrB1), is a selenium-dependent enzyme that, like other Msrs, is required for lens cell viability. In order to investigate the roles of SelR in protecting human lens epithelial (hLE) cells against damage, the influences of SelR gene knockdown on d-galactose-induced apoptosis in hLE cells were studied. The results showed that both d-galactose and SelR gene knockdown by siRNA independently induced oxidative stress. When SelR-gene-silenced hLE cells were exposed to d-galactose, glucose-regulated protein 78 (GRP78) protein level was further increased, mitochondrial membrane potential was significantly decreased and accompanied by a release of mitochondrial cytochrome c. At the same time, the apoptosis cells percentage and the caspase-3 activity were visibly elevated in hLE cells. These results suggested that SelR might protect hLE cell mitochondria and mitigating apoptosis in hLE cells against oxidative stress and endoplasmic reticulum (ER) stress induced by d-galactose, implying that selenium as a micronutrient may play important roles in hLE cells. PMID:26875981

  13. Converging or Diverging Lens?

    ERIC Educational Resources Information Center

    Branca, Mario

    2013-01-01

    Why does a lens magnify? Why does it shrink objects? Why does this happen? The activities that we propose here are useful in helping us to understand how lenses work, and they show that the same lens can have different magnification capabilities. A converging lens can also act as a diverging lens. (Contains 4 figures.)

  14. Wireless Control of an LC Adaptive Lens

    NASA Astrophysics Data System (ADS)

    Vdovin, G.; Loktev, M.; Zhang, X.

    We consider using liquid crystal adaptive lenses to correct the accommodation loss and higher-order aberrations of the human eye. In this configuration, the adaptive lens is embedded into the eye lens implant and can be controlled through a wireless inductive link. In this work we experimentally demonstrate a wireless control of a liquid crystal adaptive lens in a wide range of its focusing power by using two coupled coils with the primary coil driven from a low-voltage source through a switching control circuit and the secondary coil used to drive the lens.

  15. Foxe view of lens development and disease.

    PubMed

    Medina-Martinez, Olga; Jamrich, Milan

    2007-04-01

    The recent identification of a mutation in Foxe3 that causes congenital primary aphakia in humans marks an important milestone. Congenital primary aphakia is a rare developmental disease in which the lens does not form. Previously, Foxe3 had been shown to play a crucial role in vertebrate lens formation and this gene is one of the earliest integrators of several signaling pathways that cooperate to form a lens. In this review, we highlight recent advances that have led to a better understanding of the developmental processes and gene regulatory networks involved in lens development and disease.

  16. 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.

  17. 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. .

  18. Contact lens in keratoconus

    PubMed Central

    Rathi, Varsha M; Mandathara, Preeji S; Dumpati, Srikanth

    2013-01-01

    Contact lenses are required for the visual improvement in patients with keratoconus. Various contact lens options, such as rigid gas permeable (RGP) lenses, soft and soft toric lenses, piggy back contact lenses (PBCL), hybrid lenses and scleral lenses are availble. This article discusses about selection of a lens depending on the type of keratoconus and the fitting philosophies of various contact lenses including the starting trial lens. A Medline search was carried out for articles in the English language with the keywords keratoconus and various contact lenses such as Rose k lens, RGP lens, hybrid lens, scleral lens and PBCL. PMID:23925325

  19. The Lens Capsule

    PubMed Central

    Danysh, Brian P.; Duncan, Melinda K.

    2009-01-01

    The lens capsule is a modified basement membrane that completely surrounds the ocular lens. It is known that this extracellular matrix is important for both the structure and biomechanics of the lens in addition to providing informational cues to maintain lens cell phenotype. This review covers the development and structure of the lens capsule, lens diseases associated with mutations in extracellular matrix genes and the role of the capsule in lens function including those proposed for visual accommodation, selective permeability to infectious agents, and cell signaling. PMID:18773892

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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).

  5. 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

  6. 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.

  7. 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.

  8. Microplasma Induced Cell Morphological Changes and Apoptosis of Ex Vivo Cultured Human Anterior Lens Epithelial Cells - Relevance to Capsular Opacification.

    PubMed

    Recek, Nina; Andjelić, Sofija; Hojnik, Nataša; Filipič, Gregor; Lazović, Saša; Vesel, Alenka; Primc, Gregor; Mozetič, Miran; Hawlina, Marko; Petrovski, Goran; Cvelbar, Uroš

    2016-01-01

    Inducing selective or targeted cell apoptosis without affecting large number of neighbouring cells remains a challenge. A plausible method for treatment of posterior capsular opacification (PCO) due to remaining lens epithelial cells (LECs) by reactive chemistry induced by localized single electrode microplasma discharge at top of a needle-like glass electrode with spot size ~3 μm is hereby presented. The focused and highly-localized atmospheric pressure microplasma jet with electrode discharge could induce a dose-dependent apoptosis in selected and targeted individual LECs, which could be confirmed by real-time monitoring of the morphological and structural changes at cellular level. Direct cell treatment with microplasma inside the medium appeared more effective in inducing apoptosis (caspase 8 positivity and DNA fragmentation) at a highly targeted cell level compared to treatment on top of the medium (indirect treatment). Our results show that single cell specific micropipette plasma can be used to selectively induce demise in LECs which remain in the capsular bag after cataract surgery and thus prevent their migration (CXCR4 positivity) to the posterior lens capsule and PCO formation.

  9. Dose conversion coefficients for electron exposure of the human eye lens: calculations including a whole body phantom.

    PubMed

    Behrens, R

    2013-07-01

    In this work, conversion coefficients from electron fluence to absorbed dose to the eye lens were calculated using Monte Carlo simulations based on a detailed stylised eye model and a very simple but whole body phantom. These data supersede and complement data published earlier based on the simulation of only a single stylised eye. The new data differ from the old ones by not more than 3, 4, 7 and 16 % for angles of radiation incidence of α=0°, 15°, 30° and 45°, respectively, due to the inclusion of the whole body phantom. The data presented in the present work also complement those of a recent report of the International Commission on Radiological Protection (ICRP) (ICRP Publication 116), where conversion coefficients from electron fluence to absorbed dose to the lens of the eye are shown for solely 0°, 180° and isotropic radiation incidence (but for a much broader range of energies). In this article, values are provided for angles of incidence of 0° up to 180° in steps of 15° and for rotational geometry; no systematic deviation was observed from the values given in ICRP Publication 116 for 0° (based on the application of a bare eye) and 180° (based on the application of a voxel whole body phantom). Data are given for monoenergetic electrons from 0.1 up to 10 MeV and for a broad parallel beam geometry in vacuum.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. Lipid peroxidation and cataracts: N-acetylcarnosine as a therapeutic tool to manage age-related cataracts in human and in canine eyes.

    PubMed

    Babizhayev, Mark A; Deyev, Anatoly I; Yermakova, Valentina N; Brikman, Igor V; Bours, Johan

    2004-01-01

    primary (diene conjugates, cetodienes) lipid peroxidation (LPO) products, while in later stages there is a prevalence of LPO fluorescent end-products. A reliable increase in oxiproducts of fatty acyl content of lenticular lipids was shown by a direct gas chromatography technique producing fatty acid fluorine-substituted derivatives. The lens opacity degree correlates with the level of the LPO fluorescent end-product accumulation in its tissue, accompanied by sulfhydryl group oxidation of lens proteins due to a decrease of reduced glutathione concentration in the lens. The injection of LPO products into the vitreous has been shown to induce cataract. It is concluded that peroxide damage of the lens fibre membranes may be the initial cause of cataract development. N-acetylcarnosine (as the ophthalmic drug Can-C), has been found to be suitable for the nonsurgical prevention and treatment of age-related cataracts. This molecule protects the crystalline lens from oxidative stress-induced damage, and in a recent clinical trial it was shown to produce an effective, safe and long-term improvement in sight. When administered topically to the eye in the form of Can-C, N-acetylcarnosine functions as a time-release prodrug form of L-carnosine resistant to hydrolysis with carnosinase. N-acetylcarnosine has potential as an in vivo universal antioxidant because of its ability to protect against oxidative stress in the lipid phase of biological cellular membranes and in the aqueous environment by a gradual intraocular turnover into L-carnosine. In our study the clinical effects of a topical solution of N-acetylcarnosine (Can-C) on lens opacities were examined in patients with cataracts and in canines with age-related cataracts. These data showed that N-acetylcarnosine is effective in the management of age-related cataract reversal and prevention both in human and in canine eyes.

  16. 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.

  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. 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.

  19. 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

  20. Does infrared or ultraviolet light damage the lens?

    PubMed Central

    Söderberg, P G; Talebizadeh, N; Yu, Z; Galichanin, K

    2016-01-01

    In daylight, the human eye is exposed to long wavelength ultraviolet radiation (UVR), visible radiation and short wavelength infrared radiation (IRR). Almost all the UVR and a fraction of the IRR waveband, respectively, left over after attenuation in the cornea, is absorbed in the lens. The time delay between exposure and onset of biological response in the lens varies from immediate-to-short-to-late. After exposure to sunlight or artificial sources, generating irradiances of the same order of magnitude or slightly higher, biological damage may occur photochemically or thermally. Epidemiological studies suggest a dose-dependent association between short wavelength UVR and cortical cataract. Experimental data infer that repeated daily in vivo exposures to short wavelength UVR generate photochemically induced damage in the lens, and that short delay onset cataract after UVR exposure is photochemically induced. Epidemiology suggests that daily high-intensity short wavelength IRR exposure of workers, is associated with a higher prevalence of age-related cataract. It cannot be excluded that this effect is owing to a thermally induced higher denaturation rate. Recent experimental data rule out a photochemical effect of 1090 nm in the lens but other wavelengths in the near IRR should be investigated. PMID:26768915

  1. Socio-cultural and service delivery dimensions of maternal mortality in rural central India: a qualitative exploration using a human rights lens

    PubMed Central

    Jat, Tej Ram; Deo, Prakash R.; Goicolea, Isabel; Hurtig, Anna-Karin; San Sebastian, Miguel

    2015-01-01

    Background Despite the avoidable nature of maternal mortality, unacceptably high numbers of maternal deaths occur in developing countries. Considering its preventability, maternal mortality is being increasingly recognised as a human rights issue. Integration of a human rights perspective in maternal health programmes could contribute positively in eliminating avertable maternal deaths. This study was conducted to explore socio-cultural and service delivery–related dimensions of maternal deaths in rural central India using a human rights lens. Design Social autopsies were conducted for 22 maternal deaths during 2011 in Khargone district in central India. The data were analysed using thematic analysis. The factors associated with maternal deaths were classified by using the ‘three delays’ framework and were examined by using a human rights lens. Results All 22 women tried to access medical assistance, but various factors delayed their access to appropriate care. The underestimation of the severity of complications by family members, gender inequity, and perceptions of low-quality delivery services delayed decisions to seek care. Transportation problems and care seeking at multiple facilities delayed reaching appropriate health facilities. Negligence by health staff and unavailability of blood and emergency obstetric care services delayed receiving adequate care after reaching a health facility. Conclusions The study highlighted various socio-cultural and service delivery–related factors which are violating women's human rights and resulting in maternal deaths in rural central India. This study highlights that, despite the health system's conscious effort to improve maternal health, normative elements of a human rights approach to maternal health (i.e. availability, accessibility, acceptability, and quality of maternal health services) were not upheld. The data and analysis suggest that the deceased women and their relatives were unable to claim their

  2. Socio-cultural and service delivery dimensions of maternal mortality in rural central India: a qualitative exploration using a human rights lens.

    PubMed

    Jat, Tej Ram; Deo, Prakash R; Goicolea, Isabel; Hurtig, Anna-Karin; Sebastian, Miguel San

    2015-01-01

    Background Despite the avoidable nature of maternal mortality, unacceptably high numbers of maternal deaths occur in developing countries. Considering its preventability, maternal mortality is being increasingly recognised as a human rights issue. Integration of a human rights perspective in maternal health programmes could contribute positively in eliminating avertable maternal deaths. This study was conducted to explore socio-cultural and service delivery-related dimensions of maternal deaths in rural central India using a human rights lens. Design Social autopsies were conducted for 22 maternal deaths during 2011 in Khargone district in central India. The data were analysed using thematic analysis. The factors associated with maternal deaths were classified by using the 'three delays' framework and were examined by using a human rights lens. Results All 22 women tried to access medical assistance, but various factors delayed their access to appropriate care. The underestimation of the severity of complications by family members, gender inequity, and perceptions of low-quality delivery services delayed decisions to seek care. Transportation problems and care seeking at multiple facilities delayed reaching appropriate health facilities. Negligence by health staff and unavailability of blood and emergency obstetric care services delayed receiving adequate care after reaching a health facility. Conclusions The study highlighted various socio-cultural and service delivery-related factors which are violating women's human rights and resulting in maternal deaths in rural central India. This study highlights that, despite the health system's conscious effort to improve maternal health, normative elements of a human rights approach to maternal health (i.e. availability, accessibility, acceptability, and quality of maternal health services) were not upheld. The data and analysis suggest that the deceased women and their relatives were unable to claim their entitlements

  3. 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.

  4. Contact Lens Care

    MedlinePlus

    ... For Consumers Consumer Information by Audience For Women Contact Lens Care Share Tweet Linkedin Pin it More ... 1088, www.fda.gov/medwatch Learn More about Contact Lens Care Other Tips on Contact Lenses Decorative ...

  5. Nuclear Magnetic Resonance Structure of a Major Lens Protein, Human γC-Crystallin: Role of the Dipole Moment in Protein Solubility.

    PubMed

    Dixit, Karuna; Pande, Ajay; Pande, Jayanti; Sarma, Siddhartha P

    2016-06-07

    A hallmark of the crystallin proteins is their exceptionally high solubility, which is vital for maintaining the high refractive index of the eye lens. Human γC-crystallin is a major γ-crystallin whose mutant forms are associated with congenital cataracts but whose three-dimensional structure is not known. An earlier study of a homology model concluded that human γC-crystallin has low intrinsic solubility, mainly because of the atypical magnitude and fluctuations of its dipole moment. On the contrary, the high-resolution tertiary structure of human γC-crystallin determined here shows unequivocally that it is a highly soluble, monomeric molecule in solution. Notable differences between the orientations and interactions of several side chains are observed upon comparison to those in the model. No evidence of the pivotal role ascribed to the effect of dipole moment on protein solubility was found. The nuclear magnetic resonance structure should facilitate a comprehensive understanding of the deleterious effects of cataract-associated mutations in human γC-crystallin.

  6. 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

  7. 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

  8. 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.

  9. Nerve repulsion by the lens and cornea during cornea innervation is dependent on Robo-Slit signaling and diminishes with neuron age.

    PubMed

    Schwend, Tyler; Lwigale, Peter Y; Conrad, Gary W

    2012-03-01

    The cornea, the most densely innervated tissue on the surface of the body, becomes innervated in a series of highly coordinated developmental events. During cornea development, chick trigeminal nerve growth cones reach the cornea margin at embryonic day (E)5, where they are initially repelled for days from E5 to E8, instead encircling the corneal periphery in a nerve ring prior to entering on E9. The molecular events coordinating growth cone guidance during cornea development are poorly understood. Here we evaluated a potential role for the Robo-Slit nerve guidance family. We found that Slits 1, 2 and 3 expression in the cornea and lens persisted during all stages of cornea innervation examined. Robo1 expression was developmentally regulated in trigeminal cell bodies, expressed robustly during nerve ring formation (E5-8), then later declining concurrent with projection of growth cones into the cornea. In this study we provide in vivo and in vitro evidence that Robo-Slit signaling guides trigeminal nerves during cornea innervation. Transient, localized inhibition of Robo-Slit signaling, by means of beads loaded with inhibitory Robo-Fc protein implanted into the developing eyefield in vivo, led to disorganized nerve ring formation and premature cornea innervation. Additionally, when trigeminal explants (source of neurons) were oriented adjacent to lens vesicles or corneas (source of repellant molecules) in organotypic tissue culture both lens and cornea tissues strongly repelled E7 trigeminal neurites, except in the presence of inhibitory Robo-Fc protein. In contrast, E10 trigeminal neurites were not as strongly repelled by cornea, and presence of Robo-Slit inhibitory protein had no effect. In full, these findings suggest that nerve repulsion from the lens and cornea during nerve ring formation is mediated by Robo-Slit signaling. Later, a shift in nerve guidance behavior occurs, in part due to molecular changes in trigeminal neurons, including Robo1 downregulation

  10. Coculture with intraocular lens material-activated macrophages induces an inflammatory phenotype in lens epithelial cells.

    PubMed

    Pintwala, Robert; Postnikoff, Cameron; Molladavoodi, Sara; Gorbet, Maud

    2015-03-01

    Cataracts are the leading cause of blindness worldwide, requiring surgical implantation of an intraocular lens. Despite evidence of leukocyte ingress into the postoperative lens, few studies have investigated the leukocyte response to intraocular lens materials. A novel coculture model was developed to examine macrophage activation by hydrophilic acrylic (poly(2-hydroxyethyl methacrylate)) and hydrophobic acrylic (polymethylmethacrylate) commercial intraocular lens. The human monocytic cell line THP-1 was differentiated into macrophages and cocultured with human lens epithelial cell line (HLE-B3) with or without an intraocular lens for one, two, four, or six days. Using flow cytometry and confocal microscopy, expression of the macrophage activation marker CD54 (intercellular adhesion molecule-1) and production of reactive oxygen species via the fluorogenic probe 2',7'-dichlorodihydrofluorescein diacetate were examined in macrophages. α-Smooth muscle actin, a transdifferentiation marker, was characterized in lens epithelial cells. The poly(2-hydroxyethyl methacrylate) intraocular lens prevented adhesion but induced significant macrophage activation (p < 0.03) versus control (no intraocular lens), while the polymethylmethacrylate intraocular lens enabled adhesion and multinucleated fusion, but induced no significant activation. Coculture with either intraocular lens increased reactive oxygen species production in macrophages after one day (p < 0.03) and increased expression of α-smooth muscle actin in HLE B-3 after six days, although only poly(2-hydroxyethyl methacrylate) induced a significant difference versus control (p < 0.01). Our results imply that-contrary to prior uveal biocompatibility understanding-macrophage adherence is not necessary for a strong inflammatory response to an intraocular lens, with hydrophilic surfaces inducing higher activation than hydrophobic surfaces. These findings provide a new method of inquiry into uveal

  11. 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.

  12. 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

  13. 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.

  14. Aberration design of zoom lens systems using thick lens modules.

    PubMed

    Zhang, Jinkai; Chen, Xiaobo; Xi, Juntong; Wu, Zhuoqi

    2014-12-20

    A systematic approach for the aberration design of a zoom lens system using a thick lens module is presented. Each component is treated as a thick lens module at the beginning of the design. A thick lens module refers to a thick lens component with a real lens structure, like lens materials, lens curvatures, lens thicknesses, and lens interval distances. All nine third-order aberrations of a thick lens component are considered during the design. The relationship of component aberrations in different zoom positions can be approximated from the aberration shift. After minimizing the aberrations of the zoom lens system, the nine third-order aberrations of every lens component can be determined. Then the thick lens structure of every lens component can be determined after optimization according to their first-order properties and third-order aberration targets. After a third optimization for minimum practical third-order aberrations of a zoom lens system, the aberration design using the thick lens module is complete, which provides a practical zoom lens system with thick lens structures. A double-sided telecentric zoom lens system is designed using the thick lens module in this paper, which shows that this method is practical for zoom lens design.

  15. The Analysis of Intracellular and Intercellular Calcium Signaling in Human Anterior Lens Capsule Epithelial Cells with Regard to Different Types and Stages of the Cataract.

    PubMed

    Gosak, Marko; Markovič, Rene; Fajmut, Aleš; Marhl, Marko; Hawlina, Marko; Andjelić, Sofija

    2015-01-01

    In this work we investigated how modifications of the Ca2+ homeostasis in anterior lens epithelial cells (LECs) are associated with different types of cataract (cortical or nuclear) and how the progression of the cataract (mild or moderate) affects the Ca2+ signaling. We systematically analyzed different aspects of intra- and inter-cellular Ca2+ signaling in the human LECs, which are attached to surgically isolated lens capsule (LC), obtained during cataract surgery. We monitored the temporal and spatial changes in intracellular Ca2+ concentration after stimulation with acetylcholine by means of Fura-2 fluorescence captured with an inverted microscope. In our analysis we compared the features of Ca2+ signals in individual cells, synchronized activations, spatio-temporal grouping and the nature of intercellular communication between LECs. The latter was assessed by using the methodologies of the complex network theory. Our results point out that at the level of individual cells there are no significant differences when comparing the features of the signals with regard either to the type or the stage of the cataract. On the other hand, noticeable differences are observed at the multicellular level, despite inter-capsule variability. LCs associated with more developed cataracts were found to exhibit a slower collective response to stimulation, a less pronounced spatio-temporal clustering of LECs with similar signaling characteristics. The reconstructed intercellular networks were found to be sparser and more segregated than in LCs associated with mild cataracts. Moreover, we show that spontaneously active LECs often operate in localized groups with quite well aligned Ca2+ activity. The presence of spontaneous activity was also found to affect the stimulated Ca2+ responses of individual cells. Our findings indicate that the cataract progression entails the impairment of intercellular signaling thereby suggesting the functional importance of altered Ca2+ signaling of

  16. The Analysis of Intracellular and Intercellular Calcium Signaling in Human Anterior Lens Capsule Epithelial Cells with Regard to Different Types and Stages of the Cataract

    PubMed Central

    Gosak, Marko; Markovič, Rene; Fajmut, Aleš; Marhl, Marko; Hawlina, Marko; Andjelić, Sofija

    2015-01-01

    In this work we investigated how modifications of the Ca2+ homeostasis in anterior lens epithelial cells (LECs) are associated with different types of cataract (cortical or nuclear) and how the progression of the cataract (mild or moderate) affects the Ca2+ signaling. We systematically analyzed different aspects of intra- and inter-cellular Ca2+ signaling in the human LECs, which are attached to surgically isolated lens capsule (LC), obtained during cataract surgery. We monitored the temporal and spatial changes in intracellular Ca2+ concentration after stimulation with acetylcholine by means of Fura-2 fluorescence captured with an inverted microscope. In our analysis we compared the features of Ca2+ signals in individual cells, synchronized activations, spatio-temporal grouping and the nature of intercellular communication between LECs. The latter was assessed by using the methodologies of the complex network theory. Our results point out that at the level of individual cells there are no significant differences when comparing the features of the signals with regard either to the type or the stage of the cataract. On the other hand, noticeable differences are observed at the multicellular level, despite inter-capsule variability. LCs associated with more developed cataracts were found to exhibit a slower collective response to stimulation, a less pronounced spatio-temporal clustering of LECs with similar signaling characteristics. The reconstructed intercellular networks were found to be sparser and more segregated than in LCs associated with mild cataracts. Moreover, we show that spontaneously active LECs often operate in localized groups with quite well aligned Ca2+ activity. The presence of spontaneous activity was also found to affect the stimulated Ca2+ responses of individual cells. Our findings indicate that the cataract progression entails the impairment of intercellular signaling thereby suggesting the functional importance of altered Ca2+ signaling of

  17. Characterization of a human-pathogenic Acanthamoeba griffini isolated from a contact lens-wearing keratitis patient in Spain.

    PubMed

    Heredero-Bermejo, I; Criado-Fornelio, A; De Fuentes, I; Soliveri, J; Copa-Patiño, J L; Pérez-Serrano, J

    2015-02-01

    Amoebae were isolated from contact lenses of a symptomatic lens wearer in Spain. Protozoa were characterized by studying their morphology, biology, protease activity and the 18S rRNA gene sequence. Morphology of the organism was observed by light microscopy, scanning electron microscopy and transmission electron microscopy. Its structure corresponded to an amphizoic amoeba. The protozoa grew well at 37 °C and poorly at lower temperatures. In addition, it was capable of lysing mammalian cells in vitro. A major 56 kDa proteolytic enzyme was observed in amoeba crude extracts by gelatin-sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Most proteolytic enzymes in protozoa extracts showed significant activity over a wide range of pH (3-9) and temperature (8-45 °C) values. The assays on inhibition of protease activity indicated strongly that enzymes detected in amoeba extracts corresponded to serine proteases and, to a lesser extent, cysteine proteases. The use of proteinase inhibitors on a tissue culture model proved that the proteinase activity is critical for developing focal lesions in HeLa cell monolayers. Finally, partial sequencing of the 18S ribosomal RNA gene and phylogenetic analyses indicated that the isolate is closely related to Acanthamoeba griffini H37 from the UK (T3 genotype).

  18. An integrative lens model approach to bias and accuracy in human inferences: hindsight effects and knowledge updating in personality judgments.

    PubMed

    Nestler, Steffen; Egloff, Boris; Küfner, Albrecht C P; Back, Mitja D

    2012-10-01

    The present article integrates research on the accurate inference of personality traits with process models of hindsight bias (the tendency to exaggerate in hindsight what one had said in foresight). Specifically, the article suggests a new model that integrates assumptions of the lens model on accurate personality judgments and accounts that view hindsight effects as a by-product of knowledge updating. We suggest 3 processes that have the potential to explain the occurrence of hindsight effects in personality judgments: (a) changes in an individual's cue perceptions, (b) changes in the utilization of more valid cues, and (c) changes in the consistency with which cue knowledge is applied. In 2 studies (N1 = 91, N2 = 93), participants were presented with target pictures and were asked to judge each target's levels of the Big Five. Thereafter, they received feedback and had to recall their original judgments. Results show that there were clear hindsight effects for all 5 personality dimensions. Importantly, we found evidence that both the utilization of more valid cues and changes in cue perceptions--but not changes in the consistency with which cue knowledge is applied--account for the hindsight effects. Implications of these results for models explaining hindsight effects, the inference of personality judgments, and the accuracy of these inferences are discussed.

  19. Diffusion and Monod kinetics model to determine in vivo human corneal oxygen-consumption rate during soft contact lens wear

    PubMed Central

    Del Castillo, Luis F.; da Silva, Ana R. Ferreira; Hernández, Saul I.; Aguilella, M.; Andrio, Andreu; Mollá, Sergio; Compañ, Vicente

    2014-01-01

    Purpose We present an analysis of the corneal oxygen consumption Qc from non-linear models, using data of oxygen partial pressure or tension (pO2) obtained from in vivo estimation previously reported by other authors.1 Methods Assuming that the cornea is a single homogeneous layer, the oxygen permeability through the cornea will be the same regardless of the type of lens that is available on it. The obtention of the real value of the maximum oxygen consumption rate Qc,max is very important because this parameter is directly related with the gradient pressure profile into the cornea and moreover, the real corneal oxygen consumption is influenced by both anterior and posterior oxygen fluxes. Results Our calculations give different values for the maximum oxygen consumption rate Qc,max, when different oxygen pressure values (high and low pO2) are considered at the interface cornea-tears film. Conclusion Present results are relevant for the calculation on the partial pressure of oxygen, available at different depths into the corneal tissue behind contact lenses of different oxygen transmissibility. PMID:25649636

  20. A silent mutation in human alpha-A crystallin gene in patients with age-related nuclear or cortical cataract.

    PubMed

    Mynampati, Bharani K; Muthukumarappa, Thungapathra; Ghosh, Sujata; Ram, Jagat

    2017-02-01

    A cataract is a complex multifactorial disease that results from alterations in the cellular architecture, i.e. lens proteins. Genes associated with the development of lens include crystallin genes. Although crystallins are highly conserved proteins among vertebrates, a significant number of polymorphisms exist in human population. In this study, we screened for polymorphisms in crystallin alpha A (CRYAA) and alpha B (CRYAB) genes in 200 patients over 40 years of age, diagnosed with age-related cataract (ARC; nuclear and cortical cataracts). Genomic DNA was extracted from the peripheral blood. The coding regions of the CRYAA and CRYAB gene were amplified using polymerase chain reaction and subjected to restriction digestion. Restriction fragment length polymorphism (RFLP) was performed using known restriction enzymes for CRYAA and CRYAB genes. Denaturing high performance liquid chromatography and direct sequencing were performed to detect sequence variation in CRYAA gene. In silico analysis of secondary CRYAA mRNA structure was performed using CLC RNA Workbench. RFLP analysis did not show any changes in the restriction sites of CRYAA and CRYAB genes. In 6 patients (4 patients with nuclear cataract and 2 with cortical cataract), sequence analysis of the exon 1 in the CRYAA gene showed a silent single nucleotide polymorphism [D2D] (CRYAA: C to T transition). One of the patients with nuclear cataract was homozygous for this allele. The in silico analysis revealed that D2D mutation results in a compact CRYAA mRNA secondary structure, while the wild type CRYAA mRNA has a weak or loose secondary structure. D2D mutation in the CRYAA gene may be an additional risk factor for progression of ARC.

  1. 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

  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. 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.

  4. 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

  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. 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.

  9. 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.

  10. 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.

  11. In vitro dimensions and curvatures of human lenses.

    PubMed

    Rosen, Alexandre M; Denham, David B; Fernandez, Viviana; Borja, David; Ho, Arthur; Manns, Fabrice; Parel, Jean-Marie; Augusteyn, Robert C

    2006-03-01

    The purpose of this study was to determine dimensions and curvatures of excised human lenses using the technique of shadowphotogrammetry. A modified optical comparator and digital camera were used to photograph magnified sagittal and coronal lens profiles. Equatorial diameter, anterior and posterior sagittal thickness, anterior and posterior curvatures, and shape factors were obtained from these images. The data were used to calculate lens volumes, which were compared with the lens weights. Measurements were made on 37 human lenses ranging in age from 20 to 99 years. These showed that lens dimensions and the anterior radius of curvature increase linearly throughout adult life while posterior curvature remains constant. The relative shape (or aspect ratio) of the posterior lens is unchanged through adult life since both equatorial diameter and posterior thickness increase at the same rate. The ratio of anterior thickness to posterior thickness is constant at 0.70. It is suggested that in vivo forces alter the apparent location of the lens equator, that the in vitro lens shape corresponds to the maximally accommodated shape in vivo and that the shapes of the accommodated and unaccommodated lens progressively converge toward each other due to lens growth with age, with a convergence point located near the age of total loss of accommodation (55-60 years). Together, these observations provide additional support for the Helmholtz theory of accommodation.

  12. Analysis of the application of the generalized monod kinetics model to describe the human corneal oxygen-consumption rate during soft contact lens wear.

    PubMed

    Compañ, V; Aguilella-Arzo, M; Del Castillo, L F; Hernández, S I; Gonzalez-Meijome, J M

    2016-07-26

    This work is an analysis of the application of the generalized Monod kinetics model describing human corneal oxygen consumption during soft contact lens wear to models previously used by Chhabra et al. (J Biomed Mater Res B Appl Biomater, 2009a;90:202-209, Optom Vis Sci 2009b;86:454-466) and Larrea and Büchler (Invest Ophthalmol Vis Sci 2009;50:1076-1080). We use oxygen tension from in vivo estimations provided by Bonanno [Bonanno et al., Invest Ophthalmol Vis Sci 2002;43:371-376, and Bonanno et al 2009]. We consider four hydrogel and six silicone hydrogel lenses. The cornea is considered a single homogeneous layer, with constant oxygen permeability regardless of the type of lens worn. Our calculations yield different values for the maximum oxygen consumption rate Qc,max , whith differents oxygen tensions (high and low pc ) at the cornea-tears interface. Surprisingly, for both models, we observe an increase in oxygen consumption near an oxygen tension of 105 mmHg until a maximum is reached, then decreasing for higher levels of oxygen pressure. That is, when lowering the pressure of oxygen, the parameter Qc,max initially increases depending on the intensity of the change in pressure. Which, it could be related with the variation of the pH. Furthermore, it is also noted that to greater reductions in pressure, this parameter decreases, possibly due to changes in the concentration of glucose related to the anaerobic respiration. The averaged in vivo human corneal oxygen consumption rate of 1.47 × 10(-4) cm(3) of O2 /cm(3) tissue s, with Monod kinetics model, considering all the lenses studied, is smaller than the average oxygen consumption rate value obtained using the Larrea and Büchler model. The impact that these calculations have on the oxygen partial pressure available at different depths in the corneal tissue is presented and discussed, taking into consideration previous models used in this study. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl

  13. Introduction to the development of intraocular lens

    NASA Astrophysics Data System (ADS)

    Li, Yifan; Peng, Runling; Hu, Shuilan; Wei, Maowei; Chen, Jiabi

    2013-08-01

    In order to cure the cataract disease or injuries in eyes, intraocular lens(IOL) has been studied all the time to replace the crystalline lens in human eyes. Researches on IOL are started early from 19th century, and it develops greatly in the hundreds years after. This article introduces several main kinds of IOLs that appear in the development history of IOL, and raises the double-liquid zoom IOL based on electrowetting, which will be the trend of IOL study.

  14. 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.

  15. 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.

  16. 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.

  17. Olfactomedin-like 3 (OLFML3) gene expression in baboon and human ocular tissues: cornea, lens, uvea and retina

    PubMed Central

    Rodríguez-Sánchez, Iràm Pablo; Garza-Rodríguez, Maria Lourdes; Mohamed-Noriega, Karim; Voruganti, Venkata Saroja; Tejero, Maria Elizabeth; Delgado-Enciso, Ivan; Ibave, Diana Cristina Perez; Schlabritz-Loutsevitch, Natalia E.; Mohamed-Noriega, Jibran; Martinez-Fierro, Margarita L; Reséndez-Pérez, Diana; Cole, Shelley A; Cavazos-Adame, Humberto; Comuzzie, Anthony G.; Mohamed-Hamsho, Jesús; Barrera-Saldaña, Hugo Alberto

    2013-01-01

    Background Olfactomedin-like is a polyfunctional polymeric glycoprotein. This family has at least four members. One member of this family is OLFML3, which is preferentially expressed in placenta but is also detected in other adult tissues including the liver and heart. However, the orthologous rat gene is expressed in the iris, sclera, trabecular meshwork, retina, and optic nerve. Methods OLFML3 amplification was performed by RT-PCR from human and baboon ocular tissues. The products were cloned and sequenced. Results We report OFML3 expression in human and baboon eye. The full CDS has 1221 bp, from which a OFR of 406 amino acid was obtained. The baboon OLFML3 gene nucleotidic sequence has 98%, and amino acidic 99% similarity with humans. Conclusions OLFML3 expression in human and baboon ocular tissues and its high similarity make the baboon a powerful model to deduce the physiological and/or metabolic function of this protein in the eye. PMID:23398349

  18. Role of αA-crystallin-derived αA66-80 peptide in guinea pig lens crystallin aggregation and insolubilization

    PubMed Central

    Raju, Murugesan; Mooney, Brian P.; Thakkar, Kavi M.; Giblin, Frank J.; Schey, Kevin L.; Sharma, K. Krishna

    2015-01-01

    Earlier we reported that low molecular weight (LMW) peptides accumulate in aging human lens tissue and that among the LMW peptides, the chaperone inhibitor peptide αA66-80, derived from α-crystallin protein, is one of the predominant peptides. We showed that in vitro αA66-80 induces protein aggregation. The current study was undertaken to determine whether LMW peptides are also present in guinea pig lens tissue subjected to hyperbaric oxygen (HBO) in vivo. The nuclear opacity induced by HBO in guinea pig lens is the closest animal model for studying age-related cataract formation in humans. A LMW peptide profile by mass spectrometry showed the presence of an increased amount of LMW peptides in HBO-treated guinea pig lenses compared to age-matched controls. Interestingly, the mass spectrometric data also showed that the chaperone inhibitor peptide αA66-80 accumulates in HBO-treated guinea pig lens. Following incubation of synthetic chaperone inhibitor peptide αA66-80 with α-crystallin from guinea pig lens extracts, we observed a decreased ability of α-crystallin to inhibit the amorphous aggregation of the target protein alcohol dehydrogenase and the formation of large light scattering aggregates, similar to those we have observed with human α-crystallin and αA66-80 peptide. Further, time-lapse recordings showed that a preformed complex of α-crystallin and αA66-80 attracted additional crystallin molecules to form even larger aggregates. These results demonstrate that LMW peptide–mediated cataract development in aged human lens and in HBO-induced lens opacity in the guinea pig may have common molecular pathways. PMID:25639202

  19. 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

  20. Tear analysis in contact lens wearers.

    PubMed Central

    Farris, R L

    1985-01-01

    Tear analysis in contact lens wearers was compared with tear analysis in aphakics without contact lens wear and normal phakic patients. Subjects were divided into five groups: group 1, aphakic without contact lens; group 2, phakic with daily-wear hard contact lens; group 3, phakic with daily-wear soft contact lens; group 4, phakic with extended-wear soft contact lens; and group 5, aphakic with extended-wear soft contact lens. The experimental groups were compared with age- and sex-matched control groups for statistical analysis of tear variables by means of the Student's t-test. The variables measured were tear osmolarity, tear albumin, and lysozyme and lactoferrin concentrations in basal and reflex tears. Highly significant elevations of tear osmolarity were found in aphakic subjects without contact lenses. Less significant differences in tear osmolarity were found in phakic subjects with hard daily-wear lenses or with extended-wear soft lenses. Tear albumin, lysozyme, and lactoferrin in basal and reflex tears were not significantly different in the different groups of contact lens wearers or in the group of aphakic subjects without contact lenses compared with their control groups. Individual variations in tear albumin, lysozyme, and lactoferrin appeared to be responsible for the inability to demonstrate significant differences in tear composition in association with the wearing of different types of contact lenses. Older and aphakic patients demonstrated a tendency to have increased concentrations of proteins in the tears compared with younger, phakic contact lens wearers and normal controls without contact lenses. PMID:3914131

  1. Virtual-screening targeting Human Immunodeficiency Virus type 1 integrase-lens epithelium-derived growth factor/p75 interaction for drug development.

    PubMed

    Gu, Wan-Gang; Liu, Bai-Nan; Yuan, Jun-Fa

    2015-02-01

    Three integrase (IN) inhibitors have been approved by FDA for clinical treatment of Human Immunodeficiency Virus (HIV) infection. This stimulates more researchers to focus their studies on this target for anti-HIV drug development. Three steps regarding of IN activity have been validated for inhibitor discovery: strand transfer, 3'-terminal processing, and IN-lens epithelium-derived growth factor (LEDGF)/p75 interaction. Among them, IN-LEDGF/p75 interaction is a new target validated in recent years. Emergence of drug-resistant virus strains makes this target appealing to pharmacologists. Compared with the traditional screening methods such as AlphaScreen and cell-based screening developed for IN inhibitor discovery, virtual screening is a powerful technique in modern drug discovery. Here we summarized the recent advances of virtual-screening targeting IN-LEDFG/p75 interaction. The combined application of virtual screening and experiments in drug discovery against IN-LEDFG/p75 interaction sheds light on anti-HIV research and drug discovery.

  2. LC-MS display of the total modified amino acids in cataract lens proteins and in lens proteins glycated by ascorbic acid in vitro.

    PubMed

    Cheng, Rongzhu; Feng, Qi; Ortwerth, Beryl J

    2006-05-01

    We previously reported chromatographic evidence supporting the similarity of yellow chromophores isolated from aged human lens proteins, early brunescent cataract lens proteins and calf lens proteins ascorbylated in vitro [Cheng, R. et al. Biochimica et Biophysica Acta 1537, 14-26, 2001]. In this paper, new evidence supporting the chemical identity of the modified amino acids in these protein populations were collected by using a newly developed two-dimensional LC-MS mapping technique supported by tandem mass analysis of the major species. The pooled water-insoluble proteins from aged normal human lenses, early stage brunescent cataract lenses and calf lens proteins reacted with or without 20 mM ascorbic acid in air for 4 weeks were digested with a battery of proteolytic enzymes under argon to release the modified amino acids. Aliquots equivalent to 2.0 g of digested protein were subjected to size-exclusion chromatography on a Bio-Gel P-2 column and four major A330nm-absorbing peaks were collected. Peaks 1, 2 and 3, which contained most of the modified amino acids were concentrated and subjected to RP-HPLC/ESI-MS, and the mass elution maps were determined. The samples were again analyzed and those peaks with a 10(4) - 10(6) response factor were subjected to MS/MS analysis to identify the daughter ions of each modification. Mass spectrometric maps of peaks 1, 2 and 3 from cataract lenses showed 58, 40 and 55 mass values, respectively, ranging from 150 to 600 Da. Similar analyses of the peaks from digests of the ascorbylated calf lens proteins gave 81, 70 and 67 mass values, respectively, of which 100 were identical to the peaks in the cataract lens proteins. A total of 40 of the major species from each digest were analyzed by LC-MS/MS and 36 were shown to be identical. Calf lens proteins incubated without ascorbic acid showed several similar mass values, but the response factors were 100 to 1000-fold less for every modification. Based upon these data, we conclude

  3. Monitoring sanitation and hygiene in the 2030 Agenda for Sustainable Development: A review through the lens of human rights.

    PubMed

    Giné-Garriga, Ricard; Flores-Baquero, Óscar; Jiménez-Fdez de Palencia, Alejandro; Pérez-Foguet, Agustí

    2017-02-15

    International monitoring of drinking water and sanitation has been jointly carried out by WHO and UNICEF through their Joint Monitoring Programme (JMP). With the end of the Millennium Development Goals (MDGs) era in 2015, the JMP has proposed a post-2015 framework for integrated monitoring of water and sanitation targets included in the Sustainable Development Goal no. 6. This article discusses how each element of the proposed sanitation target and corresponding indicators can be understood from a human rights perspective. Building on the MDGs, and although some of the weaknesses and gaps persist, the discussion suggests that the post-2015 proposal is a step forward towards a monitoring framework where human rights elements related to sanitation are effectively promoted. In addition, to support the interpretation and implementation of the normative content of human rights obligations related to sanitation, the study proposes a reduced set of easy-to-assess indicators to measure the normative criteria of this right, which are then grouped in a multidimensional framework to describe increasing levels of sanitation service. To do this, the study combines literature review and specific local experience from three case studies. It is shown that the proposed monitoring tools, namely the indicators and the multidimensional indicator framework, provide guidance on monitoring the human right to sanitation. In doing so, they might ultimately help sector stakeholders in the realization of this right.

  4. 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

  5. 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

  6. Lens extraction with ultrasound. Experiments in rabbits.

    PubMed Central

    Clarkson, D M; Phillips, C I

    1976-01-01

    The extraction of the rabbit lens is described using a 25 G irrigating needle and a 22 G aspirating needle; at the latter's bevelled tip lens fragmentation occurs due to the longitudinal ultrasonic vibrations generated there--an 'acoustic horn' causes the tip to vibrate with large amplitudes. The use of small needles allows considerable manoeuvrability in the anterior chamber and usually eliminates the need for corneal suturing. Push-pull coupled syringes equate the volume of irrigation with that of aspiration. This procedure makes possible lens extraction through an aperture in the anterior capsule of the rabbit's lens and a similar machine is being constructed for trial on human cataract. Images PMID:1009054

  7. Evaluations and geometrical measurements of the human eye in order to establish the design parameters for the customized contact lens

    NASA Astrophysics Data System (ADS)

    Pascu, A. T.; Besnea, D.; Constantin, V.; Spanu, A.; Ciobanu, R.

    2016-08-01

    The paper presents the usual methods and means for geometrical evaluation and measurement for the anterior pole of the eyeball applied in studies conducted on real patients. The results were centralized, evaluated and presented in a summary in the paper. The purpose of the studies is to determine the range of dimensional values of the anterior pole of the human eyeball for the parameterization of the devices and checking tools when manufacturing the contact lenses.

  8. How the Human Eye Focuses.

    ERIC Educational Resources Information Center

    Koretz, Jane F.; Handelman, George H.

    1988-01-01

    Describes the decline in people's ability to focus their eyes as their age increases. Discusses probable causes of this effect including changes in the eye's geometry and biochemistry. Diagrammatically illustrates age related changes in the lens of the human eye. (CW)

  9. The oblique electron lens.

    NASA Technical Reports Server (NTRS)

    Johnson, C. B.; Hallam, K. L.

    1973-01-01

    An oblique electron lens is described that is especially applicable to image converters and camera tubes employing flat opaque photocathodes. The use of optical lenses, corrector plates, and/or mirrors (often employed in other electron lenses designed for use with opaque photocathodes) are eliminated. The oblique electron lens is well suited to ultraviolet and vacuum ultraviolet image converters, and to image converters employing opaque negative electron affinity photocathodes. It is also possible to use this oblique electron lens for electronography. Measurements on an experimental tube show that a limiting resolution of 50 line pairs/mm is possible, but the intrinsic lens quality is believed to approach that of a conventional electromagnetic lens having uniform and colinear electric and magnetic fields.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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?

  19. 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...

  20. 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

  1. Role of Aquaporin 0 in lens biomechanics

    SciTech Connect

    Sindhu Kumari, S.; Gupta, Neha; Shiels, Alan; FitzGerald, Paul G.; Menon, Anil G.; Mathias, Richard T.; Varadaraj, Kulandaiappan

    2015-07-10

    together they help to confer fiber cell shape, architecture and integrity. To our knowledge, this is the first report identifying the involvement of an aquaporin in lens biomechanics. Since accommodation is required in human lenses for proper focusing, alteration in the adhesion and/or water channel functions of AQP0 could contribute to presbyopia. - Highlights: • AQP0 aids in lens biomechanics. • AQP0 provides lens stiffness. • AQP0 is critical for lens transparency. • AQP0 could play a significant role in lens accommodation in human. • Alteration in the function(s) of lens AQP0 could lead to presbyopia.

  2. 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.

  3. 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

  4. MicroRNA-34a promoting apoptosis of human lens epithelial cells through down-regulation of B-cell lymphoma-2 and silent information regulator

    PubMed Central

    Li, Qing-Lan; Zhang, Hong-Yang; Qin, Yong-Jie; Meng, Qian-Li; Yao, Xiao-Lei; Guo, Hai-Ke

    2016-01-01

    AIM To investigate the role of microRNA-34a (miR-34a) in the induction of apoptosis of human lens epithelial (HLE-B3) cells. METHODS The apoptosis of HLE-B3 cells was detected by Annexin V-PE apoptosis detection kit after the treatment with 200 µmol/L H2O2 for 24h and lentiviral miR-34a vector transfection. The expression of miR-34a in the cells was quantified by quantitative real time polymerase chain reaction (qRT-PCR) in response to H2O2 exposure and the vector transfection. The effects of overexpression of miR-34a on the expression of B-cell lymphoma-2 (Bcl-2) and silent information regulator 1 (SIRT1) was determined by qRT-PCR and Western blot. RESULTS The expression of miR-34a was up-regulated by the treatment of H2O2 in HLE-B3 cells. The increased expression of miR-34a is accompanied with the cell apoptosis. Consistence with the H2O2 exposure, ectopic overexpression of miR-34a in HLE-B3 cells promoted cells apoptosis. Importantly the anti-apoptosis factors Bcl-2 and SIRT1 were reduced significantly by up-regulation of miR-34a in HLE-B3 cells. CONCLUSION MiR-34a promotes the apoptosis of HLE-B3 cells by down-regulating Bcl-2 and SIRT1, suggesting that miR-34a may involve in the pathogenesis of cataract formation and targeting miR-34a may be a potentially therapeutic approach for treatment of cataract. PMID:27990356

  5. Contact lens hygiene compliance and lens case contamination: A review.

    PubMed

    Wu, Yvonne Tzu-Ying; Willcox, Mark; Zhu, Hua; Stapleton, Fiona

    2015-10-01

    A contaminated contact lens case can act as a reservoir for microorganisms that could potentially compromise contact lens wear and lead to sight threatening adverse events. The rate, level and profile of microbial contamination in lens cases, compliance and other risk factors associated with lens case contamination, and the challenges currently faced in this field are discussed. The rate of lens case contamination is commonly over 50%. Coagulase-negative Staphylococcus, Bacillus spp., Pseudomonas aeruginosa and Serratia marcescens are frequently recovered from lens cases. In addition, we provide suggestions regarding how to clean contact lens cases and improve lens wearers' compliance as well as future lens case design for reducing lens case contamination. This review highlights the challenges in reducing the level of microbial contamination which require an industry wide approach.

  6. The lens circulation.

    PubMed

    Mathias, Richard T; Kistler, Joerg; Donaldson, Paul

    2007-03-01

    The lens is the largest organ in the body that lacks a vasculature. The reason is simple: blood vessels scatter and absorb light while the physiological role of the lens is to be transparent so it can assist the cornea in focusing light on the retina. We hypothesize this lack of blood supply has led the lens to evolve an internal circulation of ions that is coupled to fluid movement, thus creating an internal micro-circulatory system, which makes up for the lack of vasculature. This review covers the membrane transport systems that are believed to generate and direct this internal circulatory system.

  7. Unitary lens semiconductor device

    DOEpatents

    Lear, K.L.

    1997-05-27

    A unitary lens semiconductor device and method are disclosed. The unitary lens semiconductor device is provided with at least one semiconductor layer having a composition varying in the growth direction for unitarily forming one or more lenses in the semiconductor layer. Unitary lens semiconductor devices may be formed as light-processing devices such as microlenses, and as light-active devices such as light-emitting diodes, photodetectors, resonant-cavity light-emitting diodes, vertical-cavity surface-emitting lasers, and resonant cavity photodetectors. 9 figs.

  8. Unitary lens semiconductor device

    DOEpatents

    Lear, Kevin L.

    1997-01-01

    A unitary lens semiconductor device and method. The unitary lens semiconductor device is provided with at least one semiconductor layer having a composition varying in the growth direction for unitarily forming one or more lenses in the semiconductor layer. Unitary lens semiconductor devices may be formed as light-processing devices such as microlenses, and as light-active devices such as light-emitting diodes, photodetectors, resonant-cavity light-emitting diodes, vertical-cavity surface-emitting lasers, and resonant cavity photodetectors.

  9. Variations in the corneal surface temperature with contact lens wear.

    PubMed

    Ooi, E H; Ng, E Y K; Purslow, C; Acharya, R

    2007-05-01

    This paper presents the two-dimensional simulation of heat propagation in the human eye model during contact lens wear with finite element analysis. Three types of contact lens are studied: Lotrafilcon A, Balafilcon A, and Etafilcon A. The models are solved for both steady and transient solutions. The corneal surface temperature during contact lens wear is found to decrease (average, 0.52 +/- 0.05 degrees C compared with a bare cornea for all lens types). A contact lens with a higher water content has a lower steady state temperature than a contact lens with a lower water content does. Various initial temperatures for the contact lens are found to affect the first 400 s of the temperature variation. When the initial temperature is lower than the corneal temperature, a reduction in temperature is observed during contact lens insertion while the opposite is observed when the initial temperature is higher than the corneal temperature. The increase in evaporation rate when a contact lens is worn increases the cooling effect on the ocular surface. This is suggested to be the cause of lower corneal surface temperature when wearing a contact lens.

  10. Applying a gender lens on human papillomavirus infection: cervical cancer screening, HPV DNA testing, and HPV vaccination

    PubMed Central

    2013-01-01

    Background Our aim is to provide a state-of-the-art overview of knowledge on sex (biological) and gender (sociocultural) aspects of Human papillomavirus (HPV) and cervical cancer for educational purposes. Considerable disparities exist in cervical cancer incidences between different subgroups of women. We provide an outline on the crucial issues and debates based on the recent literature published in leading gender medicine journals. Intersectionality was applied in order to help categorise the knowledge. Methods Key terms (HPV, cervical cancer) were screened in Gender Medicine, Journal of Women’s Health and Women & Health from January 2005-June 2012. Additional searches were conducted for topics insufficiently mentioned, such as HPV vaccination of boys. In total, 71 publications were included (56 original papers, four reviews, six reports, three commentaries, one editorial and one policy statement). Results Research reveals complexity in the way various subgroups of women adhere to cervical screening. Less educated women, older women, uninsured women, homeless women, migrant women facing language barriers, women who have sex with women and obese women participate in Pap smears less frequently. A series of barriers can act to impede decisions to vaccinate against HPV. Conclusions Both male and female controlled preventive methods and treatment measures should be developed in order to tackle HPV infection and different strategies are needed for different subgroups. A substantial discussion and research on alternative methods of prevention was and is lacking. In future research, sex and gender aspects of HPV-related diseases of boys and men as well as subgroup differences in HPV risk need to be addressed. PMID:23394214

  11. The Assessment and Non-Pharmacologic Treatment of Procedural Pain from Infancy to School Age Through a Developmental Lens: A Synthesis of Evidence with Recommendations

    PubMed Central

    Thrane, Susan E.; Wanless, Shannon; Cohen, Susan M.; Danford, Cynthia A.

    2015-01-01

    Introduction The 2011 IOM report stated that pain management in children is often lacking especially during routine medical procedures. The purpose of this review is to bring a developmental lens to the challenges in assessment and non-pharmacologic treatment of pain in young children. Method A synthesis of the findings from an electronic search of PubMed and the university library using the keywords pain, assessment, treatment, alternative, complementary, integrative, infant, toddler, preschool, young, pediatric, and child was completed. A targeted search identified additional sources for best evidence. Results Assessment of developmental cues is essential. For example, crying, facial expression, and body posture are behaviors in infancy that indicate pain: However in toddlers these same behaviors are not necessarily indicative of pain. Preschoolers need observation scales in combination with self-report while for older children self-report is the gold standard. Pain management in infants includes swaddling and sucking. However for toddlers, preschoolers and older children, increasingly sophisticated distraction techniques such as easily implemented non-pharmacologic pain management strategies include reading stories, watching cartoons, or listening to music. Discussion A developmental approach to assessing and treating pain is critical. Swaddling, picture books, or blowing bubbles are easy and effective when used at the appropriate developmental stage and relieve both physical and emotional pain. Untreated pain in infants and young children may lead to increased pain perception and chronic pain in adolescents and adults. Continued research in the non-pharmacological treatment of pain is an important part of the national agenda. PMID:26424196

  12. Reflections From a Fresnel Lens

    ERIC Educational Resources Information Center

    Keeports, David

    2005-01-01

    Reflection of light by a convex Fresnel lens gives rise to two distinct images. A highly convex inverted real reflective image forms on the object side of the lens, while an upright virtual reflective image forms on the opposite side of the lens. I describe here a set of laser experiments performed upon a Fresnel lens. These experiments provide…

  13. 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

  14. Role of Aquaporin 0 in lens biomechanics.

    PubMed

    Sindhu Kumari, S; Gupta, Neha; Shiels, Alan; FitzGerald, Paul G; Menon, Anil G; Mathias, Richard T; Varadaraj, Kulandaiappan

    2015-07-10

    fiber cell shape, architecture and integrity. To our knowledge, this is the first report identifying the involvement of an aquaporin in lens biomechanics. Since accommodation is required in human lenses for proper focusing, alteration in the adhesion and/or water channel functions of AQP0 could contribute to presbyopia.

  15. 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.

  16. 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.

  17. Contact Lens Risks

    MedlinePlus

    ... Health and Consumer Devices Consumer Products Contact Lenses Contact Lens Risks Share Tweet Linkedin Pin it More ... redness blurred vision swelling pain Serious Hazards of Contact Lenses Symptoms of eye irritation can indicate a ...

  18. 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

  19. 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.

  20. Interferometric Lens Testing

    DTIC Science & Technology

    1976-09-01

    present tests was inspected with a Twyman -Green interferometer and found to give wavefront deviations (peak to valley) no greater than about Ü.10 X...The retro-reflecting plane mirror w&s tested on a Twyman -Green interferometer and found to give wavefront deviations (peak to valley) no greater...Interferogram scanning, lens aberrations, lens testing, optical transfer function, wavefront shearing interferometer . 10. ABSTRACT (Conllnum on

  1. Tunable Polymer Lens

    DTIC Science & Technology

    2008-08-04

    Sylgard® 184). Poly ( methyl methacrylate ) (PMMA) was provided by Atofina Chemicals, Inc. (Plexiglas V920). The SEBS copolymer and PMMA resins...convex poly ( methyl methacrylate ) (PMMA) lens, R=25.8 mm, with a tunable elastomeric lens membrane, R=38.6 mm. The PMMA is rigid; the variable focal...using a combination of deformable and rigid polymeric materials. An elastomeric styrene- ethylene /butylene-styrene (SEBS) block copolymer was

  2. Lens auto-centering

    NASA Astrophysics Data System (ADS)

    Lamontagne, Frédéric; Desnoyers, Nichola; Doucet, Michel; Côté, Patrice; Gauvin, Jonny; Anctil, Geneviève; Tremblay, Mathieu

    2015-09-01

    In a typical optical system, optical elements usually need to be precisely positioned and aligned to perform the correct optical function. This positioning and alignment involves securing the optical element in a holder or mount. Proper centering of an optical element with respect to the holder is a delicate operation that generally requires tight manufacturing tolerances or active alignment, resulting in costly optical assemblies. To optimize optical performance and minimize manufacturing cost, there is a need for a lens mounting method that could relax manufacturing tolerance, reduce assembly time and provide high centering accuracy. This paper presents a patent pending lens mounting method developed at INO that can be compared to the drop-in technique for its simplicity while providing the level of accuracy close to that achievable with techniques using a centering machine (usually < 5 μm). This innovative auto-centering method is based on the use of geometrical relationship between the lens diameter, the lens radius of curvature and the thread angle of the retaining ring. The autocentering principle and centering test results performed on real optical assemblies are presented. In addition to the low assembly time, high centering accuracy, and environmental robustness, the INO auto-centering method has the advantage of relaxing lens and barrel bore diameter tolerances as well as lens wedge tolerances. The use of this novel lens mounting method significantly reduces manufacturing and assembly costs for high performance optical systems. Large volume productions would especially benefit from this advancement in precision lens mounting, potentially providing a drastic cost reduction.

  3. Terahertz Artificial Dielectric Lens

    NASA Astrophysics Data System (ADS)

    Mendis, Rajind; Nagai, Masaya; Wang, Yiqiu; Karl, Nicholas; Mittleman, Daniel M.

    2016-03-01

    We have designed, fabricated, and experimentally characterized a lens for the THz regime based on artificial dielectrics. These are man-made media that mimic properties of naturally occurring dielectric media, or even manifest properties that cannot generally occur in nature. For example, the well-known dielectric property, the refractive index, which usually has a value greater than unity, can have a value less than unity in an artificial dielectric. For our lens, the artificial-dielectric medium is made up of a parallel stack of 100 μm thick metal plates that form an array of parallel-plate waveguides. The convergent lens has a plano-concave geometry, in contrast to conventional dielectric lenses. Our results demonstrate that this lens is capable of focusing a 2 cm diameter beam to a spot size of 4 mm, at the design frequency of 0.17 THz. The results further demonstrate that the overall power transmission of the lens can be better than certain conventional dielectric lenses commonly used in the THz regime. Intriguingly, we also observe that under certain conditions, the lens boundary demarcated by the discontinuous plate edges actually resembles a smooth continuous surface. These results highlight the importance of this artificial-dielectric technology for the development of future THz-wave devices.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. Lens epithelium and radiation cataract. III. The influence of age on the nuclear fragmentation of the meridional row cells following x irradiation

    SciTech Connect

    Worgul, B.V.; Low, S.; Merriam, G.R. Jr.

    1982-07-01

    Studies were conducted on the effect of age on the production of fragmented nuclei in meridional row (MR) cells following ocular exposure to x radiation. It was found that vulnerability to such damage is maximal approximately 4 weeks postpartum in rats, and that increasingly larger doses of x rays were required to produce equal responses in older animals. Studies on other animals (mice, rabbits, frogs) thought to be resistant to this injury indicate that the failure to see this pathological change in those species is related to age. Although its role in cataractogenesis is unclear, direct damage to the nuclei of MR cells may be ubiquitous among animals susceptible to radiation cataract development.

  9. 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.

  10. Combined Effects of Aging and HIV Infection on Semantic Verbal Fluency: A View of the Cortical Hypothesis Through the Lens of Clustering and Switching

    PubMed Central

    Iudicello, Jennifer E.; Woods, Steven Paul; Deutsch, Reena; Grant, Igor

    2012-01-01

    The profile of HIV-associated neurocognitive disorders (HAND) has classically been characterized as “subcortical”, but questions have arisen as to whether aging with HIV in the antiretroviral therapy era has subtlety shifted the expression of HAND into a more “cortical” disorder (e.g., decay of semantic memory stores). We evaluated this hypothesis by examining semantic fluency and its component processes (i.e., clustering and switching) in 257 individuals across four groups stratified by age (<40 and ≥ 50 years) and HIV serostatus. Jonckheere-Terpstra tests revealed significant monotonic trends for the combined effects of HIV and aging on overall semantic (and letter) fluency and switching, but not cluster size, with greatest deficits evident in the older adults with HIV infection. Within the older HIV-infected cohort, poorer switching was uniquely associated with self-reported declines in instrumental activities of daily living and deficits in learning and executive functions, but not semantic memory. Results suggest that HIV infection and aging may confer adverse additive effects on the executive components of semantic fluency (i.e., switching), rather than a degradation of semantic memory stores (i.e., cluster size), which is a profile that is most consistent with combined frontostriatal neuropathological burden of these two conditions. PMID:22292479

  11. 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.

  12. 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…

  13. 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...

  14. [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.

  15. 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.

  16. 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.

  17. Bio-inspired accommodating fluidic intraocular lens.

    PubMed

    Qiao, Wen; Johnson, Daniel; Tsai, Frank S; Cho, Sung Hwan; Lo, Yu-Hwa

    2009-10-15

    The invention of intraocular lens (IOL), a substitute for crystalline lens, represents a major advancement in cataract surgery. After about sixty years of IOL development, one key remaining problem is its limited accommodation range compared with natural eyes. To overcome this performance limit, we explore bio-inspired fluidic IOL. By mimicking the working principle of natural eyes, a fluidic intraocular lens can achieve an exceedingly large accommodation range. An experiment on fluidic IOL demonstrated a very high tuning range of 12 D. This accommodation range was achieved with a modest amount of force (0.06 N) and equatorial radius change (0.286 mm), in conditions matching well with the characteristics of aged eyes.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. Liquid lens: advances in adaptive optics

    NASA Astrophysics Data System (ADS)

    Casey, Shawn Patrick

    2010-12-01

    'Liquid lens' technologies promise significant advancements in machine vision and optical communications systems. Adaptations for machine vision, human vision correction, and optical communications are used to exemplify the versatile nature of this technology. Utilization of liquid lens elements allows the cost effective implementation of optical velocity measurement. The project consists of a custom image processor, camera, and interface. The images are passed into customized pattern recognition and optical character recognition algorithms. A single camera would be used for both speed detection and object recognition.

  5. 50. (no plate) Lens, lens pedestal, mercury float, drawing # ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    50. (no plate) Lens, lens pedestal, mercury float, drawing # 3101, sheet 1 of 2. Approved April 6, 1928. - Block Island Southeast Light, Spring Street & Mohegan Trail at Mohegan Bluffs, New Shoreham, Washington County, RI

  6. 51. (no plate) Lens, lens pedestal, mercury float, shade holder ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    51. (no plate) Lens, lens pedestal, mercury float, shade holder installation, drawing # 3101, sheet 2 of 2. Approved April 6, 1928. - Block Island Southeast Light, Spring Street & Mohegan Trail at Mohegan Bluffs, New Shoreham, Washington County, RI

  7. 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.

  8. Fresnel lens study

    SciTech Connect

    Not Available

    1986-05-01

    Thick film sol-gel technology was evaluated to determine the feasibility of utilizing sol-gels to produce embossable materials ultimately for the production of all-glass Fresnel optics. The feasibility study has utilized the relatively undeveloped branch of organically modified sol-gels. The results of this work shown that organically modified sol-gels posses properties which allow the formation of thick, patternable and adherent coatings. The study resulted in the fabrication of over 600 samples based on over 100 sol-gel formulations. Samples were evaluated for clarity, transmittance and other optical properties. Environmental tests were performed on selected groups. Although moderate success was obtained on producing a Fresnel lens layer bonded to glass, a fully densified lens was not achieved. The process and chemistries indicate that improvements based on these materials and techniques may lead to an acceptable all-glass Fresnel lens.

  9. Fresnel lens study

    NASA Astrophysics Data System (ADS)

    1986-05-01

    Thick film sol-gel technology was evaluated to determine the feasibility of utilizing sol-gels to produce embossable materials ultimately for the production of all-glass Fresnel optics. The feasibility study has utilized the relatively undeveloped branch of organically modified sol-gels. The results of this work show that organically modified sol-gels possess properties which allow the formation of thick, patternable and adherent coatings. The study resulted in the fabrication of over 600 samples based on over 100 sol-gel formulations. Samples were evaluated for clarity, transmittance and other optical properties. Environmental tests were performed on selected groups. Although moderate success was obtained on producing a Fresnel lens layer bonded to glass, a fully densified lens was not achieved. The process and chemistries indicate that improvements based on these materials and techniques may lead to an acceptable all-glass Fresnel lens.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. Microoptical compound lens

    DOEpatents

    Sweatt, William C.; Gill, David D.

    2007-10-23

    An apposition microoptical compound lens comprises a plurality of lenslets arrayed around a segment of a hollow, three-dimensional optical shell. The lenslets collect light from an object and focus the light rays onto the concentric, curved front surface of a coherent fiber bundle. The fiber bundle transports the light rays to a planar detector, forming a plurality of sub-images that can be reconstructed as a full image. The microoptical compound lens can have a small size (millimeters), wide field of view (up to 180.degree.), and adequate resolution for object recognition and tracking.

  15. Effects of alpha-crystallin on lens cell function and cataract pathology.

    PubMed

    Andley, Usha P

    2009-09-01

    The development of cataracts is a debilitating eye condition which is common in elderly patients and afflicts millions worldwide. Cataracts result from the deposition of aggregated proteins in the eye which causes clouding of the lens, light scattering, and obstruction of vision. Non-syndromic, hereditary human cataract development is linked to point mutations in the CRYAA and CRYAB genes which encode alphaA and alphaB-crystallin. The alpha-crystallins are small heat shock proteins which play central roles in maintaining lens transparency and refractive properties. The discovery in 1992 that these proteins possess chaperone-like activity has led most researchers to focus on the ability of alpha-crystallins to prevent protein aggregation in vitro. While the ability of alpha-crystallins to efficiently trap aggregation-prone denatured proteins in vitro is thought to delay the development of age-related cataracts in vivo, alpha-crystallins have additional functions which may also contribute to cataract pathology. In addition to chaperone activity, alpha-crystallins are known to protect cells from stress-induced apoptosis, regulate cell growth, and enhance genomic stability. They also physically and functionally interact with both the cell membrane and cytoskeleton. Functional changes in alpha-crystallin have been shown to modify membrane and cell-cell interactions and lead to lens cell pathology in vivo. This article focuses on the multiple diverse roles of alphaA-crystallin in the maintenance of lens function and cataract development in vivo.

  16. 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.

  17. Lens window simplifies TDL housing

    NASA Technical Reports Server (NTRS)

    Robinson, D. M.; Rowland, C. W.

    1979-01-01

    Lens window seal in tunable-diode-laser housing replaces plan parallel window. Lens seals housing and acts as optical-output coupler, thus eliminating need for additional reimaging or collimating optics.

  18. 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

  19. 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.

  20. Broadband Achromatic Telecentric Lens

    NASA Technical Reports Server (NTRS)

    Mouroulis, Pantazis

    2007-01-01

    A new type of lens design features broadband achromatic performance as well as telecentricity, using a minimum number of spherical elements. With appropriate modifications, the lens design form can be tailored to cover the range of response of the focal-plane array, from Si (400-1,000 nm) to InGaAs (400-1,700 or 2,100 nm) or InSb/HgCdTe reaching to 2,500 nm. For reference, lenses typically are achromatized over the visible wavelength range of 480-650 nm. In remote sensing applications, there is a need for broadband achromatic telescopes, normally satisfied with mirror-based systems. However, mirror systems are not always feasible due to size or geometry restrictions. They also require expensive aspheric surfaces. Non-obscured mirror systems can be difficult to align and have a limited (essentially one-dimensional) field of view. Centrally obscured types have a two-dimensional but very limited field in addition to the obscuration. Telecentricity is a highly desirable property for matching typical spectrometer types, as well as for reducing the variation of the angle of incidence and cross-talk on the detector for simple camera types. This rotationally symmetric telescope with no obscuration and using spherical surfaces and selected glass types fills a need in the range of short focal lengths. It can be used as a compact front unit for a matched spectrometer, as an ultra-broadband camera objective lens, or as the optics of an integrated camera/spectrometer in which the wavelength information is obtained by the use of strip or linear variable filters on the focal plane array. This kind of camera and spectrometer system can find applications in remote sensing, as well as in-situ applications for geological mapping and characterization of minerals, ecological studies, and target detection and identification through spectral signatures. Commercially, the lens can be used in quality-control applications via spectral analysis. The lens design is based on the rear landscape

  1. 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.

  2. 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

  3. 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.

  4. Amounts of phospholipids and cholesterol in lipid domains formed in intact lens membranes: methodology development and its application to studies of porcine lens membranes

    PubMed Central

    Raguz, Marija; Mainali, Laxman; O'Brien, William J.; Subczynski, Witold K.

    2015-01-01

    An electron paramagnetic resonance spin-labeling method has been developed that allows quantitative evaluation of the amounts of phospholipids and cholesterol in lipid domains of intact fiber-cell plasma membranes isolated from cortical and nuclear regions of eye lenses. The long term goal of this research is the assessment of organizational changes in human lens fiber cell membranes that occur with age and during cataract development. The measurements needed to be performed on lens membranes prepared from eyes of single donors and from single eyes. For these types of studies it is necessary to separate the age/cataract related changes from preparation/technique related changes. Human lenses differ not only because of age, but also because of the varying health histories of the donors. To solve these problems the sample-to-sample preparation/technique related changes were evaluated for cortical and nuclear lens membranes prepared from single porcine eyes. It was assumed that the differences due to the age (animals were two year old) and environmental conditions for raising these animals were minimal. Mean values and standard deviations from preparation/technique changes for measured amounts of lipids in membrane domains were calculated. Statistical analysis (Student's t test) of the data also allowed determining the differences of mean values which were statistically significant with P ≤ 0.05. These differences defined for porcine lenses will be used for comparison of amounts of lipids in domains in human lens membranes prepared from eyes of single donors and from single eyes. Greater separations will indicate that differences were statistically significant with (P ≤ 0.05) and that they came from different than preparation/technique sources. Results confirmed that in nuclear porcine membranes the amounts of lipids in domains created due to the presence of membrane proteins were greater than those in cortical membranes and the differences were larger than the

  5. Amounts of phospholipids and cholesterol in lipid domains formed in intact lens membranes: Methodology development and its application to studies of porcine lens membranes.

    PubMed

    Raguz, Marija; Mainali, Laxman; O'Brien, William J; Subczynski, Witold K

    2015-11-01

    An electron paramagnetic resonance spin-labeling method has been developed that allows quantitative evaluation of the amounts of phospholipids and cholesterol in lipid domains of intact fiber-cell plasma membranes isolated from cortical and nuclear regions of eye lenses. The long term goal of this research is the assessment of organizational changes in human lens fiber cell membranes that occur with age and during cataract development. The measurements needed to be performed on lens membranes prepared from eyes of single donors and from single eyes. For these types of studies it is necessary to separate the age/cataract related changes from preparation/technique related changes. Human lenses differ not only because of age, but also because of the varying health histories of the donors. To solve these problems the sample-to-sample preparation/technique related changes were evaluated for cortical and nuclear lens membranes prepared from single porcine eyes. It was assumed that the differences due to the age (animals were two year old) and environmental conditions for raising these animals were minimal. Mean values and standard deviations from preparation/technique changes for measured amounts of lipids in membrane domains were calculated. Statistical analysis (Student's t-test) of the data also allowed determining the differences of mean values which were statistically significant with P ≤ 0.05. These differences defined for porcine lenses will be used for comparison of amounts of lipids in domains in human lens membranes prepared from eyes of single donors and from single eyes. Greater separations will indicate that differences were statistically significant with (P ≤ 0.05) and that they came from different than preparation/technique sources. Results confirmed that in nuclear porcine membranes the amounts of lipids in domains created due to the presence of membrane proteins were greater than those in cortical membranes and the differences were larger than

  6. 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.

  7. 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

  8. Luneburg lens in silicon photonics.

    PubMed

    Di Falco, Andrea; Kehr, Susanne C; Leonhardt, Ulf

    2011-03-14

    The Luneburg lens is an aberration-free lens that focuses light from all directions equally well. We fabricated and tested a Luneburg lens in silicon photonics. Such fully-integrated lenses may become the building blocks of compact Fourier optics on chips. Furthermore, our fabrication technique is sufficiently versatile for making perfect imaging devices on silicon platforms.

  9. A Tribute to Len Barton

    ERIC Educational Resources Information Center

    Tomlinson, Sally

    2010-01-01

    This article constitutes a short personal tribute to Len Barton in honour of his work and our collegial relationship going back over 30 years. It covers how Len saw his intellectual project of providing critical sociological and political perspectives on special education, disability and inclusion, and his own radical political perspectives. Len's…

  10. 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...

  11. 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.

  12. Down-Regulation of MicroRNA-133b Suppresses Apoptosis of Lens Epithelial Cell by Up-Regulating BCL2L2 in Age-Related Cataracts

    PubMed Central

    Zhang, Feng; Meng, Weizhe; Tong, Bin

    2016-01-01

    Background MicroRNA-133b (miR-133b) has been reported to be involved in many diseases, including ovarian cancer and osteosarcoma. Accumulating evidence suggests that miR-133b plays important roles in human disease. In this study, we aimed to investigate the molecular mechanism, including the potential regulator and signaling pathways, of BCL2L2. Material/Methods We first searched the online miRNA database (www.mirdb.org) using the “seed sequence” located within the 3′-UTR of the target gene, and then performed luciferase assay to test the regulatory relationship between miR-133b and BCL2L2. Western blot and real-time PCR were used to determine the expression of BCL2L2 in human samples or cells treated with miRNA mimics or inhibitors. Flow cytometry was conducted to evaluate the apoptosis status of the cells. Results We validated BCL2L2 to be the direct gene using a luciferase reporter assay. We also conducted real-time PCR and Western blot analyses to study the mRNA and protein expression level of BCL2L2 among different groups (control: n=29, cataract: n=33) or cells treated with scramble control, miR-133b mimics, BCL2L2 siRNA, and miR-133b inhibitors, and identified the negative regulatory relationship between miR-133b and BCL2L2. We also conducted experiments to investigate the influence of miR-133b and BCL2L2 on the viability and apoptosis of cells. The results showed that miR-133b positively interfered with the viability of cells, while BCL2L2 negatively interfered with the viability of cells, and that miR-133b inhibited apoptosis while BCL2L2 accelerated apoptosis. Conclusions BCL2L2 was the virtual target of miR-133b, and we found a negative regulatory relationship between miR-133b and BCL2L2. MiR-133b and BCL2L2 interfered with the viability and apoptosis of cells. PMID:27802259

  13. The Lens of Chemistry

    ERIC Educational Resources Information Center

    Thalos, Mariam

    2013-01-01

    Chemistry possesses a distinctive theoretical lens--a distinctive set of theoretical concerns regarding the dynamics and transformations of a perplexing variety of organic and nonorganic substances--to which it must be faithful. Even if it is true that chemical facts bear a special (reductive) relationship to physical facts, nonetheless it will…

  14. Thin Lens Ray Tracing.

    ERIC Educational Resources Information Center

    Gatland, Ian R.

    2002-01-01

    Proposes a ray tracing approach to thin lens analysis based on a vector form of Snell's law for paraxial rays as an alternative to the usual approach in introductory physics courses. The ray tracing approach accommodates skew rays and thus provides a complete analysis. (Author/KHR)

  15. Oxygen transport through soft contact lens and cornea: Lens characterization and metabolic modeling

    NASA Astrophysics Data System (ADS)

    Chhabra, Mahendra

    The human cornea requires oxygen to sustain metabolic processes critical for its normal functioning. Any restriction to corneal oxygen supply from the external environment (e.g., by wearing a low oxygen-permeability contact lens) can lead to hypoxia, which may cause corneal edema (swelling), limbal hyperemia, neovascularization, and corneal acidosis. The need for adequate oxygen to the cornea is a major driving force for research and development of hypertransmissible soft contact lenses (SCLs). Currently, there is no standard technique for measuring oxygen permeability (Dk) of hypertransmissible silicone-hydrogel SCLs. In this work, an electrochemistry-based polarographic apparatus was designed, built, and operated to measure oxygen permeability in hypertransmissible SCLs. Unlike conventional methods where a range of lens thickness is needed for determining oxygen permeabilities of SCLs, this apparatus requires only a single lens thickness. The single-lens permeameter provides a reliable, efficient, and economic tool for measuring oxygen permeabilities of commercial hypertransmissible SCLs. The single-lens permeameter measures not only the product Dk, but, following modification, it measures separately diffusivity, D, and solubility, k, of oxygen in hypertransmissible SCLs. These properties are critical for designing better lens materials that ensure sufficient oxygen supply to the cornea. Metabolism of oxygen in the cornea is influenced by contact-lens-induced hypoxia, diseases such as diabetes, surgery, and drug treatment, Thus, estimation of the in-vivo corneal oxygen consumption rate is essential for gauging adequate oxygen supply to the cornea. Therefore, we have developed an unsteady-state reactive-diffusion model for the cornea-contact-lens system to determine in-vivo human corneal oxygen-consumption rate. Finally, a metabolic model was developed to determine the relation between contact-lens oxygen transmissibility (Dk/L) and corneal oxygen deficiency. A

  16. 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

  17. Gradient-index crystalline lens model: A new method for determining the paraxial properties by the axial and field rays

    NASA Astrophysics Data System (ADS)

    Rama, María. Angeles; Pérez, María. Victoria; Bao, Carmen; Flores-Arias, María. Teresa; Gómez-Reino, Carlos

    2005-05-01

    Gradient-index (GRIN) models of the human lens have received wide attention in optometry and vision sciences for considering the effect of inhomogeneity of the refractive index on the optical properties of the lens. This paper uses the continuous asymmetric bi-elliptical model to determine analytically cardinal elements, magnifications and refractive power of the lens by the axial and field rays in order to study the paraxial light propagation through the human lens from its GRIN nature.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. Myopia Progression over Three Years of Soft Contact Lens Wear

    PubMed Central

    Blacker, Adam; Mitchell, G. Lynn; Bullimore, Mark. A.; Long, Bill; Dillehay, Sally M.; Bergenske, Peter; Donshik, Peter; Secor, Glenda; Yoakum, John; Chalmers, Robin L

    2009-01-01

    Purpose To analyze the effect of lens material alone on myopia progression in a multi-center non-randomized prospective study of daily wear hydrogel and continuous wear silicone hydrogel contact lenses. Methods Refractive error data from completing subjects was collected during a 3-year study of 54 subjects wearing low Dk/t hydrogel contact lenses for daily wear and 230 wearing silicone hydrogel contact lenses for up to 30 nights continuous wear. Univariate analysis of refractive error changes was first conducted on factors of lens type, age at baseline, and baseline refractive error. Multivariate analysis was then performed to control for potential confounders of age (categorical by decade and continuous), and baseline refractive error. Results Multivariate analysis showed that refractive error changes were significantly affected by lens type (F = 78.2, p < 0.001, R2 = 0.218) and subject age (F = 13.1.2, p < 0.001, R2 = 0.319), but not baseline refractive error (F = 2.56, p = 0.11, R2 = 0.009). The model’s overall R2 value is 0.376; the age-adjusted refractive error changes are +0.02 D for the silicone hydrogel contact lens wearers and 0.41 D for the hydrogel contact lenses for the 3-year follow-up period. Conclusions Subject age and lens type significantly influenced the degree of myopic progression, with younger subjects and low Dk/t hydrogel contact lens wearers increasing more during the study. The Lotrafilcon A silicone hydrogel lens material may contribute to less myopia progression in adult contact lens wearers. PMID:19741563

  8. 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.

  9. 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.

  10. 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.

  11. Lens epithelial cell apoptosis and intracellular Ca2+ increase in the presence of xanthurenic acid

    PubMed Central

    Malina, Halina; Richter, Christoph; Frueh, Beatrice; Hess, Otto M

    2002-01-01

    Background Xanthurenic acid is an endogenous product of tryptophan degradation by indoleamine 2,3-dioxygenase (IDO). We have previously reported that IDO is present in mammalian lenses, and xanthurenic acid is accumulated in the lenses with aging. Here, we studied the involvement of xanthurenic acid in the human lens epithelial cell physiology. Methods Human lens epithelial cells primary cultures were used. Control cells, and cells in the presence of xanthurenic acid grow in the dark. Western blot analysis and immunofluorescence studies were performed. Results In the presence of xanthurenic acid human lens epithelial cells undergo apoptosis-like cell death. In the control cells gelsolin stained the perinuclear region, whereas in the presence of 10 μM xanthurenic acid gelsolin is translocated to the cytoskeleton, but does not lead to cytoskeleton breakdown. In the same condition caspase-3 activation, and DNA fragmentation was observed. At low (5 to 10 μM) of xanthurenic acid concentration, the elongation of the cytoskeleton was associated with migration of mitochondria and cytochrome c release. At higher concentrations xanthurenic acid (20 μM and 40 μM) damaged mitochondria were observed in the perinuclear region, and nuclear DNA cleavage was observed. We observed an induction of calpain Lp 82 and an increase of free Ca2+ in the cells in a xanthurenic acid concentration-dependent manner. Conclusions The results show that xanthurenic acid accumulation in human lens epithelial cells disturbs the normal cell physiology and leads to a cascade of pathological events. Xanthurenic acid induces calpain Lp82 and caspases in the cells growing in the dark and can be involved in senile cataract development. PMID:11934353

  12. 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…

  13. 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...

  14. 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

  15. 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

  16. OCT 3-D surface topography of isolated human crystalline lenses

    PubMed Central

    Sun, Mengchan; Birkenfeld, Judith; de Castro, Alberto; Ortiz, Sergio; Marcos, Susana

    2014-01-01

    Quantitative 3-D Optical Coherence Tomography was used to measure surface topography of 36 isolated human lenses, and to evaluate the relationship between anterior and posterior lens surface shape and their changes with age. All lens surfaces were fitted to 6th order Zernike polynomials. Astigmatism was the predominant surface aberration in anterior and posterior lens surfaces (accounting for ~55% and ~63% of the variance respectively), followed by spherical terms, coma, trefoil and tetrafoil. The amount of anterior and posterior surface astigmatism did not vary significantly with age. The relative angle between anterior and posterior surface astigmatism axes was on average 36.5 deg, tended to decrease with age, and was >45 deg in 36.1% lenses. The anterior surface RMS spherical term, RMS coma and 3rd order RMS decreased significantly with age. In general, there was a statistically significant correlation between the 3rd and 4th order terms of the anterior and posterior surfaces. Understanding the coordination of anterior and posterior lens surface geometries and their topographical changes with age sheds light into the role of the lens in the optical properties of the eye and the lens aging mechanism. PMID:25360371

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Novel Scanning Lens Instrument for Evaluating Fresnel Lens Performance: Equipment Development and Initial Results (Presentation)

    SciTech Connect

    Herrero, R.; Miller, D. C.; Kurtz, S. R.; Anton, I.; Sala, G.

    2013-07-01

    A system dedicated to the optical transmittance characterization of Fresnel lenses has been developed at NREL, in collaboration with the UPM. The system quantifies the optical efficiency of the lens by generating a performance map. The shape of the focused spot may also be analyzed to understand change in the lens performance. The primary instrument components (lasers and CCD detector) have been characterized to confirm their capability for performing optical transmittance measurements. Measurements performed on SoG and PMMA lenses subject to a variety of indoor conditions (e.g., UV and damp heat) identified differences in the optical efficiency of the evaluated lenses, demonstrating the ability of the Scanning Lens Instrument (SLI) to distinguish between the aged lenses.

  12. A novel scanning lens instrument for evaluating Fresnel lens performance: Equipment development and initial results

    NASA Astrophysics Data System (ADS)

    Herrero, Rebeca; Miller, David C.; Kurtz, Sarah R.; Antón, Ignacio; Sala, Gabriel

    2013-09-01

    A system dedicated to the optical transmittance characterization of Fresnel lenses has been developed at NREL, in collaboration with the UPM. The system quantifies the optical efficiency of the lens by generating a performance map. The shape of the focused spot may also be analyzed to understand change in the lens performance. The primary instrument components (lasers and CCD detector) have been characterized to confirm their capability for performing optical transmittance measurements. Measurements performed on SoG and PMMA lenses subject to a variety of indoor conditions (e.g., UV and damp heat) identified differences in the optical efficiency of the evaluated lenses, demonstrating the ability of the Scanning Lens Instrument (SLI) to distinguish between the aged lenses.

  13. Microplasma Induced Cell Morphological Changes and Apoptosis of Ex Vivo Cultured Human Anterior Lens Epithelial Cells – Relevance to Capsular Opacification

    PubMed Central

    Hojnik, Nataša; Filipič, Gregor; Lazović, Saša; Vesel, Alenka; Primc, Gregor; Mozetič, Miran; Hawlina, Marko; Petrovski, Goran; Cvelbar, Uroš

    2016-01-01

    Inducing selective or targeted cell apoptosis without affecting large number of neighbouring cells remains a challenge. A plausible method for treatment of posterior capsular opacification (PCO) due to remaining lens epithelial cells (LECs) by reactive chemistry induced by localized single electrode microplasma discharge at top of a needle-like glass electrode with spot size ~3 μm is hereby presented. The focused and highly-localized atmospheric pressure microplasma jet with electrode discharge could induce a dose-dependent apoptosis in selected and targeted individual LECs, which could be confirmed by real-time monitoring of the morphological and structural changes at cellular level. Direct cell treatment with microplasma inside the medium appeared more effective in inducing apoptosis (caspase 8 positivity and DNA fragmentation) at a highly targeted cell level compared to treatment on top of the medium (indirect treatment). Our results show that single cell specific micropipette plasma can be used to selectively induce demise in LECs which remain in the capsular bag after cataract surgery and thus prevent their migration (CXCR4 positivity) to the posterior lens capsule and PCO formation. PMID:27832099

  14. Effects of white light-emitting diode (LED) light exposure with different correlated color temperatures (CCTs) on human lens epithelial cells in culture.

    PubMed

    Xie, Chen; Li, Xiuyi; Tong, Jianping; Gu, Yangshun; Shen, Ye

    2014-01-01

    Cataract is the major cause for legal blindness in the world. Oxidative stress on the lens epithelial cells (hLECs) is the most important factor in cataract formation. Cumulative light-exposure from widely used light-emitting diodes (LEDs) may pose a potential oxidative threat to the lens epithelium, due to the high-energy blue light component in the white-light emission from diodes. In the interest of perfecting biosafety standards for LED domestic lighting, this study analyzed the photobiological effect of white LED light with different correlated color temperatures (CCTs) on cultured hLECs. The hLECs were cultured and cumulatively exposed to multichromatic white LED light with CCTs of 2954, 5624, and 7378 K. Cell viability of hLECs was measured by Cell Counting Kit-8 (CCK-8) assay. DNA damage was determined by alkaline comet assay. Intracellular reactive oxygen species (ROS) generation, cell cycle, and apoptosis were quantified by flow cytometry. Compared with 2954 and 5624 K LED light, LED light having a CCT of 7378 K caused overproduction of intracellular ROS and severe DNA damage, which triggered G2 /M arrest and apoptosis. These results indicate that white LEDs with a high CCT could cause significant photobiological damage to hLECs.

  15. Foveated endoscopic lens

    PubMed Central

    Hagen, Nathan

    2012-01-01

    Abstract. We present a foveated miniature endoscopic lens implemented by amplifying the optical distortion of the lens. The resulting system provides a high-resolution region in the central field of view and low resolution in the outer fields, such that a standard imaging fiber bundle can provide both the high resolution needed to determine tissue health and the wide field of view needed to determine the location within the inspected organ. Our proof of concept device achieves 7∼8  μm resolution in the fovea and an overall field of view of 4.6 mm. Example images and videos show the foveated lens’ capabilities. PMID:22463022

  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. Gradient Index Lens Research.

    DTIC Science & Technology

    1982-11-25

    over six to nine readings at two to three input polarizations each. The first set of index values is calculated assuming ei = 450 These values are...TECHNICAL REPORT RG-CR-84-2 Sli GRADIENT INDEX LENS RESEARCH Prepared by: Duncan T. Moore The Institute of Optics University of Rochester Rochester...CLASSIFICATION OF THIS PAGE (Miten Data Fntered) READ INSTRUCTIONSREPORT DOCUMENTATION PAGE BEFORE COMPLETING FORM 1. REPORT NU14MU R GOVT ACCESSION No. 3

  19. Calculation of crystalline lens power in chickens with a customized version of Bennett's equation.

    PubMed

    Iribarren, Rafael; Rozema, Jos J; Schaeffel, Frank; Morgan, Ian G

    2014-03-01

    This paper customizes Bennett's equation for calculating lens power in chicken eyes from refraction, keratometry and biometry. Previously published data on refraction, corneal power, anterior chamber depth, lens thickness, lens radii of curvature, axial length and eye power in chickens aged 10-90 days were used to estimate Gullstrand's lens power and Bennett's lens power for chicken eyes, and to calculate the lens equivalent refractive index. Bennett's A and B constants for the front and back surface powers of the lens were calculated for data measured from day 10 to 90 at 10 day intervals, and mean customized constants were calculated. The mean customized constants for Bennett's equation for chicks were A=0.574±0.023 and B=0.379±0.021. As found previously, lens power decreases with age in chicks, while corneal power decreases and axial length increases. The lens equivalent refractive index decreases with age from 10 to 90 days after hatching. Bennett's equation can be used to calculate lens power in chicken eyes for studies on animal myopia, using standard biometry.

  20. 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

  1. 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

  2. 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 ag