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Sample records for aging human lens

  1. Effect of Mild Heating on Human Lens Epithelial Cells: A Possible Model of Lens Aging

    PubMed Central

    Zhang, Keke; Zhu, Xiangjia; Lu, Yi

    2016-01-01

    This study aims to investigate the effect of mild heating on lens epithelial cells and to explore its possibility as an in vitro model for lens aging. Human lens epithelial cells (LECs) were heated at 50 °C for a cellular lens aging study. Analysis of the head group order of lens membranes was performed using Laurdan labeling. Immunofluorescence was performed to detect changes in α-crystallin expression and its cellular distribution. The chaperone-like activity of α-crystallin was also assessed. After mild heating, α-crystallin in LECs showed a tendency towards accumulation around the nucleus. The membrane head group environment of lens epithelial cells became more fluid with increasing time of exposure to mild heating, as indicated by increased water penetration. Furthermore, the chaperone activity of α-crystallin decreased, and suggests a relatively lower protective effect on other functional proteins in LECs. Thus, compared to the mild heating model based on lens tissue, this cellular model could provide a more convenient and accurate method for studying lens aging in vitro, including changes in membrane head group order in each cell, the real-time observation of crystallin distribution, and the monitoring of functional changes in the chaperone activity of crystallins as a result of aging. PMID:27725687

  2. Age and the transmittance of the human crystalline lens.

    PubMed Central

    Weale, R A

    1988-01-01

    1. Conflicting data both on the transmission of the human crystalline lens in the ultra-violet part of the spectrum and on its variation with age necessitate a re-examination of the subject. 2. Twenty-four excised lenses in the age range of 0-85 years were studied with a Perkin-Elmer spectrophotometer between 327 and 700 nm. 3. Some lenses were homogenized and the homogenates were similarly examined. 4. A systematic increase in absorbance with age was observed both in the visible and the ultra-violet parts of the spectrum. 5. An exponential function describes the data, facilitating comparison with, and prediction of, other values. 6. The absorbance of homogenized material was found to be predictable from that of intact lenses, and does not support the notion that mechanical trauma may account for high values in earlier studies. PMID:3411488

  3. AGEs in human lens capsule promote the TGFβ2-mediated EMT of lens epithelial cells: implications for age-associated fibrosis.

    PubMed

    Raghavan, Cibin T; Smuda, Mareen; Smith, Andrew J O; Howell, Scott; Smith, Dawn G; Singh, Annapurna; Gupta, Pankaj; Glomb, Marcus A; Wormstone, Ian Michael; Nagaraj, Ram H

    2016-06-01

    Proteins in basement membrane (BM) are long-lived and accumulate chemical modifications during aging; advanced glycation endproduct (AGE) formation is one such modification. The human lens capsule is a BM secreted by lens epithelial cells. In this study, we have investigated the effect of aging and cataracts on the AGE levels in the human lens capsule and determined their role in the epithelial-to-mesenchymal transition (EMT) of lens epithelial cells. EMT occurs during posterior capsule opacification (PCO), also known as secondary cataract formation. We found age-dependent increases in several AGEs and significantly higher levels in cataractous lens capsules than in normal lens capsules measured by LC-MS/MS. The TGFβ2-mediated upregulation of the mRNA levels (by qPCR) of EMT-associated proteins was significantly enhanced in cells cultured on AGE-modified BM and human lens capsule compared with those on unmodified proteins. Such responses were also observed for TGFβ1. In the human capsular bag model of PCO, the AGE content of the capsule proteins was correlated with the synthesis of TGFβ2-mediated α-smooth muscle actin (αSMA). Taken together, our data imply that AGEs in the lens capsule promote the TGFβ2-mediated fibrosis of lens epithelial cells during PCO and suggest that AGEs in BMs could have a broader role in aging and diabetes-associated fibrosis. PMID:26853893

  4. 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.

  5. Effects of senescent lens epithelial cells on the severity of age-related cortical cataract in humans

    PubMed Central

    Fu, Qiuli; Qin, Zhenwei; Yu, Jiexin; Yu, Yinhui; Tang, Qiaomei; Lyu, Danni; Zhang, Lifang; Chen, Zhijian; Yao, Ke

    2016-01-01

    Abstract The aging of lens progenitor cell has been repeatedly proposed to play a key role in age-related cataracts (ARCs), but the mechanism is far from being understood. The present study aims to investigate the relationship between aging of lens progenitor/epithelial cells and the 4 subtypes of ARCs in humans. Lens capsules, which were collected from ARC patients during surgery, were divided into 3 groups according to the age of patients (50–60, 60–80, and >80 years). The expressions of lens progenitor cell-related markers Sox2, Abcg2, and Ki67 were first examined in human lens epithelial cells (HLECs) in situ. Then, the percentage of senescent and SA-β-gal+ HLECs isolated from lens capsules were quantified. Finally, the potential relationships between the percentage of senescent (and SA-β-gal+) HLECs and the severity of ARCs were analyzed. Ki67+, Sox2+, and Abcg2+ HLECs in lens capsules were clearly more abundant in young people than in patients older than 50 years, and they were almost absent in patients older than 60 years. The percentage of primary HLECs with aging morphology increased with age, consistent with the results of SA-β-gal+ primary HLECs. Only cortical cataract classification was found to be strongly related to the percentage of SA-β-gal+ and senescent HLECs. Our study gave the initial evidence on the dynamical change of lens stem/progenitor cells in human lens capsule with age and suggested that lens progenitor/epithelial cell aging is important in the severity of cortical cataracts. PMID:27336873

  6. 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

  7. 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.

  8. AGE-RAGE interaction in the TGFβ2-mediated epithelial to mesenchymal transition of human lens epithelial cells.

    PubMed

    Raghavan, Cibin T; Nagaraj, Ram H

    2016-08-01

    Basement membrane (BM) proteins accumulate chemical modifications with age. One such modification is glycation, which results in the formation of advanced glycation endproducts (AGEs). In a previous study, we reported that AGEs in the human lens capsule (BM) promote the TGFβ2-mediated epithelial-to-mesenchymal transition (EMT) of lens epithelial cells, which we proposed as a mechanism for posterior capsule opacification (PCO) or secondary cataract formation. In this study, we investigated the role of a receptor for AGEs (RAGE) in the TGFβ2-mediated EMT in a human lens epithelial cell line (FHL124). RAGE was present in FHL124 cells, and its levels were unaltered in cells cultured on either native or AGE-modified BM or upon treatment with TGFβ2. RAGE overexpression significantly enhanced the TGFβ2-mediated EMT responses in cells cultured on AGE-modified BM compared with the unmodified matrix. In contrast, treatment of cells with a RAGE antibody or EN-RAGE (an endogenous ligand for RAGE) resulted in a significant reduction in the TGFβ2-mediated EMT response. This was accompanied by a reduction in TGFβ2-mediated Smad signaling and ROS generation. These results imply that the interaction of matrix AGEs with RAGE plays a role in the TGFβ2-mediated EMT of lens epithelial cells and suggest that the blockade of RAGE could be a strategy to prevent PCO and other age-associated fibrosis. PMID:27263094

  9. 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

  10. 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

  11. Human lens coloration and aging. Evidence for crystallin modification by the major ultraviolet filter, 3-hydroxy-kynurenine O-beta-D-glucoside.

    PubMed

    Hood, B D; Garner, B; Truscott, R J

    1999-11-12

    The human lens becomes increasingly yellow with age and thereby reduces our perception of blue light. This coloration is associated with lens proteins (crystallins), but its molecular basis was unknown. Here we show that the coloration occurs because of the interaction of crystallins with a UV filter compound, 3-hydroxykynurenine glucoside (3-OHKG). Crystallin modification results from deamination of the 3-OHKG amino acid side chain, yielding an unsaturated ketone that is susceptible to nucleophilic attack by cysteine, histidine, and lysine residues. This novel protein modification contributes to age-related lens coloration and may play a role in human nuclear cataractogenesis. PMID:10551806

  12. 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.

  13. 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-.

  14. A dimensionless ordered pull-through model of the mammalian lens epithelium evidences scaling across species and explains the age-dependent changes in cell density in the human lens

    PubMed Central

    Wu, Jun Jie; Wu, Weiju; Tholozan, Frederique M.; Saunter, Christopher D.; Girkin, John M.; Quinlan, Roy A.

    2015-01-01

    We present a mathematical (ordered pull-through; OPT) model of the cell-density profile for the mammalian lens epithelium together with new experimental data. The model is based upon dimensionless parameters, an important criterion for inter-species comparisons where lens sizes can vary greatly (e.g. bovine (approx. 18 mm); mouse (approx. 2 mm)) and confirms that mammalian lenses scale with size. The validated model includes two parameters: β/α, which is the ratio of the proliferation rate in the peripheral and in the central region of the lens; and γGZ, a dimensionless pull-through parameter that accounts for the cell transition and exit from the epithelium into the lens body. Best-fit values were determined for mouse, rat, rabbit, bovine and human lens epithelia. The OPT model accounts for the peak in cell density at the periphery of the lens epithelium, a region where cell proliferation is concentrated and reaches a maximum coincident with the germinative zone. The β/α ratio correlates with the measured FGF-2 gradient, a morphogen critical to lens cell survival, proliferation and differentiation. As proliferation declines with age, the OPT model predicted age-dependent changes in cell-density profiles, which we observed in mouse and human lenses. PMID:26236824

  15. 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

  16. The elastic constants of the human lens.

    PubMed

    Fisher, R F

    1971-01-01

    1. When the lens is spun around its antero-posterior polar axis in an apparatus designed for the purpose, high speed photography can be used to record its changing profile. By this method a variable radial centrifugal force can be applied to the lens which mimics the pull of the zonule.2. If the lens is not stressed at its centre beyond 100 Nm(-2) it behaves as a truly elastic body. When stressed beyond this limit visco-elastic strain is produced at its poles.3. The human lens has isotropic elastic properties at the extremes of life, but at the other times Young's Modulus of Elasticity varies with the direction in which it is measured.4. Young's Modulus of Elasticity of the lens varies with age, polar elasticity and equatorial elasticity, at birth being 0.75 x 10(3) and 0.85 x 10(3) Nm(-2) respectively, while at 63 years of age both are equal to 3 x 10(3) Nm(-2).5. A comparison of Young's Modulus of the young human lens with that of the rabbit and cat shows that the polar elasticity of the lenses of these animals was 5 times greater in the young rabbit, and 21 times greater in the adult cat. Equatorial elasticities of the rabbit and human lens were equal, while in the cat the equatorial elasticity was four times greater.6. A mathematical model showing the lens substance possessing a nucleus of lower isotropic elasticity than that of the isotropic elastic cortex surrounding it, accounts for the difference between polar and equatorial elasticity of the intact adult lens.7. The implications of these findings are discussed in relation to:(i) accommodation and the rheological properties of the lens;(ii) possible differences in the physical state of the lenticular proteins in the cortex and nucleus which may account for the senile variations in Young's Modulus of Elasticity in these regions of the lens;(iii) the loss of accommodation due solely to an increase in Young's Modulus of Elasticity of the lens between the ages of 15 and 60. This would amount to 44% of the total

  17. The elastic constants of the human lens

    PubMed Central

    Fisher, R. F.

    1971-01-01

    1. When the lens is spun around its antero-posterior polar axis in an apparatus designed for the purpose, high speed photography can be used to record its changing profile. By this method a variable radial centrifugal force can be applied to the lens which mimics the pull of the zonule. 2. If the lens is not stressed at its centre beyond 100 Nm-2 it behaves as a truly elastic body. When stressed beyond this limit visco-elastic strain is produced at its poles. 3. The human lens has isotropic elastic properties at the extremes of life, but at the other times Young's Modulus of Elasticity varies with the direction in which it is measured. 4. Young's Modulus of Elasticity of the lens varies with age, polar elasticity and equatorial elasticity, at birth being 0·75 × 103 and 0·85 × 103 Nm-2 respectively, while at 63 years of age both are equal to 3 × 103 Nm-2. 5. A comparison of Young's Modulus of the young human lens with that of the rabbit and cat shows that the polar elasticity of the lenses of these animals was 5 times greater in the young rabbit, and 21 times greater in the adult cat. Equatorial elasticities of the rabbit and human lens were equal, while in the cat the equatorial elasticity was four times greater. 6. A mathematical model showing the lens substance possessing a nucleus of lower isotropic elasticity than that of the isotropic elastic cortex surrounding it, accounts for the difference between polar and equatorial elasticity of the intact adult lens. 7. The implications of these findings are discussed in relation to: (i) accommodation and the rheological properties of the lens; (ii) possible differences in the physical state of the lenticular proteins in the cortex and nucleus which may account for the senile variations in Young's Modulus of Elasticity in these regions of the lens; (iii) the loss of accommodation due solely to an increase in Young's Modulus of Elasticity of the lens between the ages of 15 and 60. This would amount to 44% of the

  18. 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

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

    2011-07-15

    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. Postmortem human eyes obtained in the USA (n=46, age=6-83 years) and India (n=91, age=1 day-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 2mm 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 age

  19. Evidence of Highly Conserved β-Crystallin Disulfidome that Can be Mimicked by In Vitro Oxidation in Age-related Human Cataract and Glutathione Depleted Mouse Lens.

    PubMed

    Fan, Xingjun; Zhou, Sheng; Wang, Benlian; Hom, Grant; Guo, Minfei; Li, Binbin; Yang, Jing; Vaysburg, Dennis; Monnier, Vincent M

    2015-12-01

    Low glutathione levels are associated with crystallin oxidation in age-related nuclear cataract. To understand the role of cysteine residue oxidation, we used the novel approach of comparing human cataracts with glutathione-depleted LEGSKO mouse lenses for intra- versus intermolecular disulfide crosslinks using 2D-PAGE and proteomics, and then systematically identified in vivo and in vitro all disulfide forming sites using ICAT labeling method coupled with proteomics. Crystallins rich in intramolecular disulfides were abundant at young age in human and WT mouse lens but shifted to multimeric intermolecular disulfides at older age. The shift was ∼4x accelerated in LEGSKO lens. Most cysteine disulfides in β-crystallins (except βA4 in human) were highly conserved in mouse and human and could be generated by oxidation with H(2)O(2), whereas γ-crystallin oxidation selectively affected γC23/42/79/80/154, γD42/33, and γS83/115/130 in human cataracts, and γB79/80/110, γD19/109, γF19/79, γE19, γS83/130, and γN26/128 in mouse. Analysis based on available crystal structure suggests that conformational changes are needed to expose Cys42, Cys79/80, Cys154 in γC; Cys42, Cys33 in γD, and Cys83, Cys115, and Cys130 in γS. In conclusion, the β-crystallin disulfidome is highly conserved in age-related nuclear cataract and LEGSKO mouse, and reproducible by in vitro oxidation, whereas some of the disulfide formation sites in γ-crystallins necessitate prior conformational changes. Overall, the LEGSKO mouse model is closely reminiscent of age-related nuclear cataract.

  20. In vivo human crystalline lens topography

    PubMed Central

    Ortiz, Sergio; Pérez-Merino, Pablo; Gambra, Enrique; de Castro, Alberto; Marcos, Susana

    2012-01-01

    Custom high-resolution high-speed anterior segment spectral domain optical coherence tomography (OCT) was used to characterize three-dimensionally (3-D) the human crystalline lens in vivo. The system was provided with custom algorithms for denoising and segmentation of the images, as well as for fan (scanning) and optical (refraction) distortion correction, to provide fully quantitative images of the anterior and posterior crystalline lens surfaces. The method was tested on an artificial eye with known surfaces geometry and on a human lens in vitro, and demonstrated on three human lenses in vivo. Not correcting for distortion overestimated the anterior lens radius by 25% and the posterior lens radius by more than 65%. In vivo lens surfaces were fitted by biconicoids and Zernike polynomials after distortion correction. The anterior lens radii of curvature ranged from 10.27 to 14.14 mm, and the posterior lens radii of curvature ranged from 6.12 to 7.54 mm. Surface asphericities ranged from −0.04 to −1.96. The lens surfaces were well fitted by quadrics (with variation smaller than 2%, for 5-mm pupils), with low amounts of high order terms. Surface lens astigmatism was significant, with the anterior lens typically showing horizontal astigmatism (Z22 ranging from −11 to −1 µm) and the posterior lens showing vertical astigmatism (Z22 ranging from 6 to 10 µm). PMID:23082289

  1. Ageing of glutathione reductase in the lens.

    PubMed

    Zhang, W Z; Augusteyn, R C

    1994-07-01

    The distribution of glutathione reductase activity in concentric layers from the lens has been determined as a function of age for 16 species. Primate lenses have almost ten times the level of glutathione reductase found in other species. Comparison with the activity of hexokinase revealed that this is not due to a higher overall rate of metabolism in these lenses. By contrast, the higher activity found in bird and fish lenses reflects a higher metabolic activity in these tissues. In all species, a gradient of activity was observed with the highest specific activity in the outermost cortical fibres, decreasing to virtually no activity in the inner parts of the tissue. No alterations were found in this gradient with increasing age, other than an increase in the amount of nuclear tissue essentially devoid of activity. The maximum activity in the outer cortical fibres was the same, regardless of the age of the lens. The time taken, in different species, for the specific activity to decrease by half, was estimated from the rate of protein accumulation. This time was found to vary from a few days to several years, indicating that the decrease in activity is not due to ageing but rather, it is related to the maturation of fibre cells. These observations are discussed in terms of current concepts of lens ageing and cataract formation. PMID:7835401

  2. 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

  3. Elastic constants of the human lens capsule.

    PubMed

    Fisher, R F

    1969-03-01

    1. A technique is described whereby the elasticity of the human lens capsule has been determined at birth and throughout life. This technique requires three separate determinations: (a) thickness; (b) stress and strain; (c) Poisson's ratio; (a) the capsule was clamped between accurately perforated ground glass plates and its thickness determined by noting the change in depth of focus between Latex spherules adhering to its upper and lower surfaces; (b) the undisturbed capsule was then placed in a specially designed glass distension apparatus and the relationship between volume and pressure recorded when it was distended with isotonic saline. The permeability of the capsule was also measured; (c) in some cases Poisson's ratio was determined by measuring the change of thickness of the capsule and the height to which it rose when distended with isotonic saline at different pressures. An apparatus was designed for this purpose.2. The average thickness of the anterior capsule increases from birth until about the 60th year but thereafter it decreases slightly.3. Poisson's ratio was about 0.47 for both cat and human capsule, and no significant variations with age in human capsule could be detected.4. Corrected volume pressure curves obeyed Hook's law almost to the point of capsule rupture.5. In childhood Young's Modulus of elasticity is about 6 x 10(7) dyn/cm(2) and decreases to 3 x 10(7) dyn/cm(2) at 60 and 1.5 x 10(7) dyn/cm(2) in extreme old age.6. The ultimate tensile stress was 2.3 x 10(7) dyn/cm(2) in young capsules and 0.7 x 10(7) dyn/cm(2) in old ones. The maximum percentage elongation was 29 per cent and independent of age.7. The implications of these findings are discussed in relation to(a) the mechanical properties of the lens capsule;(b) the ageing of the lens capsule and basement membranes; and(c) the decrease in elasticity of the lens capsule as a cause of presbyopia.

  4. 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

  5. FEM simulation of the human lens compared to ex vivo porcine lens cutting pattern: a possible treatment of presbyopia

    NASA Astrophysics Data System (ADS)

    Ripken, T.; Breitenfeld, P.; Fromm, M.; Oberheide, U.; Gerten, G.; Lubatschowski, H.

    2006-02-01

    The most probable reason for presbyopia is an age related loss of elasticity of the lens. It progresses typically during the whole life and at the age of about 45 it leads to a considerable loss of the ability to accommodate within the next decade. However, both, the ciliary muscle and the lens capsule stay active and elastic, respectively. With respect to this, one concept is to regain the deformability of the lens without changing the capsule or zonular apparatus. Since the investigations of Ripken et al. proofed that the flexibility of the presbyopic lens tissue can be increased through the creation of fs-laser induced microcuts inside the lens, this is one possible approach to treat presbyopia. On this account a finite-element-method model with ANSYS of the human lens during accommodation will be presented. The analysis premises all lens materials to be linear elastic and allow large displacements. A first analysis of this method for the treatment of presbyopia is accomplished. Therefore the mechanical analysis of untreated and treated lens are compared. In addition ex-vivo elasticity measurements of untreated and treated lenses will be presented. As a result an improvement of the flexibility of the lens tissue is found and as its consequence a change of the lens radii of curvature is established. After suitable processing of the output data the change in optical power between untreated and treated lenses are calculated. The finite element simulation shows similar behaviour compared to the treated porcine lenses.

  6. 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.

  7. 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.

  8. Shape of the isolated ex-vivo human crystalline lens

    PubMed Central

    Urs, Raksha; Manns, Fabrice; Ho, Arthur; Borja, David; Amelinckx, Adriana; Smith, Jared; Jain, Rakhi; Augusteyn, Robert; Parel, Jean-Marie

    2009-01-01

    Purpose To develop an age-dependent mathematical model of the isolated ex-vivo human crystalline lens shape to serve as basis for use in computational modeling. Methods Profiles of whole isolated human lenses (n=27) aged 6 to 82, were measured from shadow-photogrammetric images. Two methods were used to analyze the lenses. In the Two-Curves Method (TCM) the anterior and posterior surfaces of the lens were fit to 10th-order even polynomials and in the One-Curve Method (OCM) the contour of one half-meridional section of the lens was fit to 10th-order polynomials. The age-dependence of the polynomial coefficients was assessed. The analysis was used to produce an age-dependent polynomial model of the whole lens shape. Results The root mean squared errors for the fits ranged from 11 to 70 μm for the OCM, 9 to 27 μm for the posterior surface of the TCM and 8 to 134 μm for the anterior surface of the TCM. The coefficients of the OCM did not display a significant trend with age. The 2nd, 6th and 10th-order coefficients of the anterior surface of the TCM decreased with age while the 8th-order coefficient increased. For the posterior surface of the TCM, the 8th-order coefficient significantly decreased with age and the 10th-order coefficient increased. The age-dependent equations of both the models provide a reliable model from age 20 to 60. The OCM model can be used for lenses older than 60 as well. Conclusion The shape of the whole human crystalline lens can be accurately modeled with 10th-order polynomial functions. These models can serve to improve computational modeling, such as finite element (FE) modeling of crystalline lenses. PMID:18950656

  9. 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

    2015-01-01

    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. PMID:25760082

  10. 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.

  11. 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

  12. 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

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

    PubMed

    Sheil, Conor J; Goncharov, Alexander V

    2016-05-01

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

  14. [Representation and mathematical analysis of human crystalline lens].

    PubMed

    Tălu, Stefan; Giovanzana, Stefano; Tălu, Mihai

    2011-01-01

    The surface of human crystalline lens can be described and analyzed using mathematical models based on parametric representations, used in biomechanical studies and 3D solid modeling of the lens. The mathematical models used in lens biomechanics allow the study and the behavior of crystalline lens on variables and complex dynamic loads. Also, the lens biomechanics has the potential to improve the results in the development of intraocular lenses and cataract surgery. The paper presents the most representative mathematical models currently used for the modeling of human crystalline lens, both optically and biomechanically.

  15. 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

  16. Optomechanical Response of Human and Monkey Lenses in a Lens Stretcher

    PubMed Central

    Manns, Fabrice; Parel, Jean-Marie; Denham, David; Billotte, Christian; Ziebarth, Noel; Borja, David; Fernandez, Viviana; Aly, Mohammed; Arrieta, Esdras; Ho, Arthur; Holden, Brien

    2012-01-01

    Purpose To quantify the forces necessary to change the shape and optical power of human and monkey lenses. Methods Cynomolgus monkey (n = 48; age: 3.8–11 years), rhesus monkey (n = 35; age: 0.7–17 years) and human (n = 20, age 8–70 years) eyes obtained postmortem, including the lens, capsule, zonules, ciliary body, and sclera were mounted in an optomechanical lens-stretching system. Starting at zero load, the lenses were symmetrically stretched in a stepwise fashion in 0.25- or 0.5-mm steps. The load, lens diameter, inner ciliary body diameter, and lens power were measured at each step and the diameter- and power-load responses were quantified. Results The diameter- and power-load responses were found to be linear in the physiologically relevant range of stretching. The average change in cynomolgus, rhesus, and human lens diameter, respectively, was 0.094, 0.109, and 0.069 mm/g in young lenses, and 0.069, 0.067, and 0.036, mm/g in older lenses. For the same lenses, the average change in lens power was −3.73, −2.83, and −1.22 D/g in young lenses and −2.46, − 2.16, and −0.49 D/g in older lenses. Conclusions The force necessary to change the lens diameter and lens power increases with age in human and monkey lenses. The results agree with the Helmholtz theory of accommodation and with presbyopia theories that predict that the force required to disaccommodate the lens increases with age. PMID:17591897

  17. Coherent fiber optic sensor for early detection of cataractogenesis in a human eye lens

    NASA Technical Reports Server (NTRS)

    Dhadwal, Harbans S.; Ansari, Rafat R.; Dellavecchia, Michael A.

    1993-01-01

    A lensless backscatter fiber optic probe is used to measure the size distribution of protein molecules inside an excised, but intact, human eye lens. The fiber optic probe, about 5 mm in diameter, can be positioned arbitrarily close to the anterior surface of the eye; it is a trans-receiver, which delivers a Gaussian laser beam into a small region inside the lens and provides a coherent detection of the laser light scattered by the protein molecules in the backward direction. Protein sizes determined from the fast and slow diffusion coefficients show good correlation with the age of the lens and cataractogenesis.

  18. 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

  19. Age-dependent lens changes in galactose-fed dogs.

    PubMed

    Lackner, P A; Rodriguez, L; Sato, S; Lizak, M J; Wyman, M; Kador, P F

    1997-03-01

    Aldose reductase initiated sugar cataract formation in 9-month old galactose-fed dogs has been documented to progress from an accentuation of lens sutures (1 month after initial feeding) to the appearance of cortical vacuoles (3 months), cortical opacities (4-6 months) and eventually the progressive formation of a clear zone at the cortical equatorial regions of the cataractous lenses (> 12 months). Here, the effect of age on the onset and degree of sugar cataract formation has been investigated in beagles fed a 30% galactose diet starting at 2, 6, and 24 months of age. Cataract formation was monitored by slit lamp and retroillumination microscopy. Compared to 9-month old dogs, cataract formation in the younger dogs was more rapid and the lens changes were more severe. In the 2-month old group of dogs, galactose-feeding resulted in a rapid formation of dense cataracts which began to resorb after 106 days of galactose feeding with only opaque nuclear remnants remaining after eight months. These changes were mirrored by age-dependent reductions of lenticular NADPH-dependent reductase activity.

  20. 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

  1. 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.

  2. 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

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

    PubMed

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

    2015-10-13

    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.

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

    PubMed

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

    2015-10-13

    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

  5. A noninvasive video-based method for measuring lens transmission properties of the human eye.

    PubMed

    Johnson, C A; Howard, D L; Marshall, D; Shu, H

    1993-11-01

    The Lens Absorption Monitor (LAM) is an automated video-based system for obtaining rapid objective noninvasive measurements of the spectral transmission properties of the human lens. The technique is based on intensity measurements of the 4th Purkinje image for different wavelengths, and incorporates several features that overcome some of the difficulties associated with previous studies using this approach. LAM transmission measures for the visible spectrum can be obtained in approximately 2 s, and in most instances can be obtained without having to dilate the subject's eye. This paper describes the technique and presents our initial findings for 40 normal observers between the ages of 24 and 77 years. Results of the LAM technique show that it is able to measure the wavelength-dependent properties of the lens accurately and to identify age-related changes in "yellowing" of the lens. Test-retest reliability of the LAM is better than for psychophysical estimates of ocular media transmission. LAM and psychophysical measures in the same subjects were found to be correlated, although LAM measures produced consistently lower values of lens density than the psychophysical determinations. There was only moderate agreement between LAM and psychophysical measures of lens density. Possible explanations for these differences are discussed. Future research will determine whether this technique is able to detect and quantify early cataract development.

  6. Epithelial cell-fibre coupling in the equator of the human lens.

    PubMed

    van Marle, J; Vrensen, G F

    1996-01-01

    A detailed freeze fracture study of human lenses of various ages revealed that coupling between epithelial cells and fibres occurs only in a limited area in the equator of the lens; it also demonstrated that the extent of coupling is independent of age. The developing fibres remain coupled to their original neighbours and no other contacts between epithelial cells and fibres appear to be established.

  7. 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

  8. Role of the human lens gradient-index profile in the compensation of third-order ocular aberrations

    NASA Astrophysics Data System (ADS)

    Díaz, José A.; Fernández-Dorado, José; Sorroche, Francisco

    2012-07-01

    The open question regarding the compensation of the ocular aberrations between the cornea and the lens is currently being investigated. We report additional insights considering the role of the lens gradient-index (GRIN) profile in third-order ocular aberrations, since this profile changes through life. Thus, we have calculated the contribution of that profile to the ocular aberrations with aging by applying the Seidel third-order theory of tilted and decentered elements, and by using a schematic-eye model. The results show the GRIN profile is needed to account for the decoupling of the aberrations between the cornea and the lens because the geometrical changes of the ocular surfaces with aging are not enough. Therefore, the current developments of aging human-eye models, as well as the experimental studies, cannot neglect the changes of the lens GRIN structure through life when modelling mechanisms of the compensation of ocular aberrations.

  9. 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®.

  10. Biodemography of human ageing

    PubMed Central

    Vaupel, James W.

    2014-01-01

    Human senescence has been delayed by a decade. This finding, documented in 1994 and bolstered since, is a fundamental discovery about the biology of human ageing, and one with profound implications for individuals, society and the economy. Remarkably, the rate of deterioration with age seems to be constant across individuals and over time: it seems that death is being delayed because people are reaching old age in better health. Research by demographers, epidemiologists and other biomedical researchers suggests that further progress is likely to be made in advancing the frontier of survival — and healthy survival — to even greater ages. PMID:20336136

  11. Phototoxicity and cytotoxicity of fullerol in human lens epithelial cells

    SciTech Connect

    Roberts, Joan E. Wielgus, Albert R. Boyes, William K. Andley, Usha Chignell, Colin F.

    2008-04-01

    The water-soluble, hydroxylated fullerene [fullerol, nano-C{sub 60}(OH){sub 22-26}] has several clinical applications including use as a drug carrier to bypass the blood ocular barriers. We have assessed fullerol's potential ocular toxicity by measuring its cytotoxicity and phototoxicity induced by UVA and visible light in vitro with human lens epithelial cells (HLE B-3). Accumulation of nano-C{sub 60}(OH){sub 22-26} in the cells was confirmed spectrophotometrically at 405 nm and cell viability estimated using MTS and LDH assays. Fullerol was cytotoxic to HLE B-3 cells maintained in the dark at concentrations higher than 20 {mu}M. Exposure to either UVA or visible light in the presence of > 5 {mu}M fullerol-induced phototoxic damage. When cells were pretreated with non-toxic antioxidants: 20 {mu}M lutein, 1 mM N-acetyl cysteine, or 1 mM L-ascorbic acid prior to irradiation, only the singlet oxygen quencher-lutein significantly protected against fullerol photodamage. Apoptosis was observed in lens cells treated with fullerol whether or not the cells were irradiated, in the order UVA > visible light > dark. Dynamic light scattering (DLS) showed that in the presence of the endogenous lens protein {alpha}-crystallin, large aggregates of fullerol were reduced. In conclusion, fullerol is both cytotoxic and phototoxic to human lens epithelial cells. Although the acute toxicity of water-soluble nano-C{sub 60}(OH){sub 22-26} is low, these compounds are retained in the body for long periods, raising concern for their chronic toxic effect. Before fullerols are used to deliver drugs to the eye, they should be tested for photo- and cytotoxicity in vivo.

  12. Human senile cataractous lens protease. Isolation and some chemical characteristics

    PubMed Central

    Swanson, Arnold A.; Nichols, John T.

    1971-01-01

    A proteolytic enzyme was isolated from human senile cataractous lens by anion-exchange and gel-filtration chromatography. Sedimentation and zone-electrophoretic experiments indicated a high degree of homogeneity for the enzyme. A molecular weight of 27000 was calculated from measurements of sedimentation velocity and diffusion coefficient. Chelating agents decreased activity which could be restored by addition of certain bivalent metal ions. Di-isopropyl phosphorofluoridate and phenylmethanesulphonyl fluoride inhibit the proteolytic activities. Optimum rates of hydrolysis were observed at pH5.2. ImagesFig. 6. PMID:5144759

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Age-Related True Exfoliation of the Lens Capsule: Phacoemulsification Surgery Results

    PubMed Central

    Ng, Alex Lap Ki; Marcet, Marcus M.; Lai, Jimmy S.M.; Yeung, Jane C.C.

    2015-01-01

    Historically associated with glassblowers, true exfoliation of the crystalline lens involves a splitting or delamination of the capsule. We reviewed the phacoemulsification records of a single surgeon for patients with true exfoliation of the lens capsule. The incidence in our series was 2.2% (6 in 278 cases). The average age was 85.0 years. All patients had successful phacoemulsification outcomes, which may have been due to accurate recognition of the condition and appropriate surgical planning. Our findings support the notion that true exfoliation may be more often associated with advanced age rather than infrared radiation. PMID:26955340

  18. EGCG prevents tryptophan oxidation of cataractous ocular lens human γ-crystallin in presence of H2O2.

    PubMed

    Chaudhury, Susmitnarayan; Ghosh, Ishita; Saha, Gautam; Dasgupta, Swagata

    2015-01-01

    Disruption of the short range order of proteins present in the ocular lens leads to cataract resulting in a loss of transparency. Human γ-crystallin (HGC), a water soluble protein present in the lens is known to aggregate with aging. A modified form of HGC (HGC(c)) was isolated from cataractous human ocular lens extract and the number of Trp residues that undergo oxidation was determined. The extent of oxidized Trp (N-formyl kynurenine) in HGC due to cataract formation was determined, primarily using fluorescence spectroscopy. The ability of (-)-epigallocatechin gallate (EGCG) to retain its antioxidant effect even in the presence of H2O2 was investigated. This was monitored by its ability to prevent the modification of intact Trp residues in HGC(c) isolated from cataractous human eye lens. Significant Trp fluorescence quenching occurs on interaction of the green tea component, EGCG with HGC(c) accompanied by a red shift. Docking studies were employed to substantiate the experimental results. As eye lens proteins are prone to oxidative stress it is essential that a clear understanding of the effects of the components generated in vivo vis-à-vis the antioxidant effects of natural polyphenols be obtained. PMID:25841365

  19. Age-dependence of the average and equivalent refractive indices of the crystalline lens

    PubMed Central

    Charman, W. Neil; Atchison, David A.

    2013-01-01

    Lens average and equivalent refractive indices are required for purposes such as lens thickness estimation and optical modeling. We modeled the refractive index gradient as a power function of the normalized distance from lens center. Average index along the lens axis was estimated by integration. Equivalent index was estimated by raytracing through a model eye to establish ocular refraction, and then backward raytracing to determine the constant refractive index yielding the same refraction. Assuming center and edge indices remained constant with age, at 1.415 and 1.37 respectively, average axial refractive index increased (1.408 to 1.411) and equivalent index decreased (1.425 to 1.420) with age increase from 20 to 70 years. These values agree well with experimental estimates based on different techniques, although the latter show considerable scatter. The simple model of index gradient gives reasonable estimates of average and equivalent lens indices, although refinements in modeling and measurements are required. PMID:24466474

  20. Age-dependence of the average and equivalent refractive indices of the crystalline lens.

    PubMed

    Charman, W Neil; Atchison, David A

    2013-12-01

    Lens average and equivalent refractive indices are required for purposes such as lens thickness estimation and optical modeling. We modeled the refractive index gradient as a power function of the normalized distance from lens center. Average index along the lens axis was estimated by integration. Equivalent index was estimated by raytracing through a model eye to establish ocular refraction, and then backward raytracing to determine the constant refractive index yielding the same refraction. Assuming center and edge indices remained constant with age, at 1.415 and 1.37 respectively, average axial refractive index increased (1.408 to 1.411) and equivalent index decreased (1.425 to 1.420) with age increase from 20 to 70 years. These values agree well with experimental estimates based on different techniques, although the latter show considerable scatter. The simple model of index gradient gives reasonable estimates of average and equivalent lens indices, although refinements in modeling and measurements are required. PMID:24466474

  1. An attempt to age mallards using eye lens proteins

    USGS Publications Warehouse

    Henny, C.J.; Ludke, J.L.

    1974-01-01

    An analysis of insoluble protein content of eye lenses from 59 known-age mallards (Anas platyrhynchos) indicated a slight increase between 8-9 months and 7 years of age. Nearly a complete overlapping of the insoluble protein content of individuals of different ages was apparent showing that the technique cannot be used to separate adult year classes of mallards. These results are contrary to findings reported for selected mammalian species; a possible explanation for the dissimilarity is discussed.

  2. 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.

  3. A PVA/PVP hydrogel for human lens substitution: Synthesis, rheological characterization, and in vitro biocompatibility.

    PubMed

    Leone, Gemma; Consumi, Marco; Greco, Giuseppe; Bonechi, Claudia; Lamponi, Stefania; Rossi, Claudio; Magnani, Agnese

    2011-05-01

    To overcome opacification and absence of accommodation of human lens substitutes a new poly(vinyl alcohol) (PVA)/poly(N-vinyl-2- pyrrolidinone) (PVP) based hydrogel (PPS31075) was realised. The Infrared Spectroscopy and the mechanical spectra confirmed the successful occurrence of crosslinking reaction. The rheological analysis pointed out a behavior comparable with that of young human lens in terms of complex shear modulus and accommodation capability. Further analysis in terms of optical properties, water content measurements, diffusion coefficient, cytotoxicity, and human capsular cell adhesion confirmed the applicability of such a hydrogel as potential human lens substitute.

  4. 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.

  5. 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.

  6. αA-Crystallin Peptide 66SDRDKFVIFLDVKHF80 Accumulating in Aging Lens Impairs the Function of α-Crystallin and Induces Lens Protein Aggregation

    PubMed Central

    Santhoshkumar, Puttur; Raju, Murugesan; Sharma, K. Krishna

    2011-01-01

    Background The eye lens is composed of fiber cells that are filled with α-, β- and γ-crystallins. The primary function of crystallins is to maintain the clarity of the lens through ordered interactions as well as through the chaperone-like function of α-crystallin. With aging, the chaperone function of α-crystallin decreases, with the concomitant accumulation of water-insoluble, light-scattering oligomers and crystallin-derived peptides. The role of crystallin-derived peptides in age-related lens protein aggregation and insolubilization is not understood. Methodology/Principal Findings We found that αA-crystallin-derived peptide, 66SDRDKFVIFLDVKHF80, which accumulates in the aging lens, can inhibit the chaperone activity of α-crystallin and cause aggregation and precipitation of lens crystallins. Age-related change in the concentration of αA-(66-80) peptide was estimated by mass spectrometry. The interaction of the peptide with native crystallin was studied by multi-angle light scattering and fluorescence methods. High molar ratios of peptide-to-crystallin were favourable for aggregation and precipitation. Time-lapse recordings showed that, in the presence of αA-(66-80) peptide, α-crystallin aggregates and functions as a nucleus for protein aggregation, attracting aggregation of additional α-, β- and γ-crystallins. Additionally, the αA-(66-80) peptide shares the principal properties of amyloid peptides, such as β-sheet structure and fibril formation. Conclusions/Significance These results suggest that crystallin-derived peptides such as αA-(66-80), generated in vivo, can induce age-related lens changes by disrupting the structure and organization of crystallins, leading to their insolubilization. The accumulation of such peptides in aging lenses may explain a novel mechanism for age-related crystallin aggregation and cataractogenesis. PMID:21552534

  7. Role of the lens capsule on the mechanical accommodative response in a lens stretcher

    PubMed Central

    Ziebarth, Noël M.; Borja, David; Arrieta, Esdras; Aly, Mohamed; Manns, Fabrice; Dortonne, Isabelle; Nankivil, Derek; Jain, Rakhi; Parel, Jean-Marie

    2009-01-01

    Purpose To determine if changes in elastic properties of the lens capsule ex vivo with age contribute to the forces required to accommodate. Methods Post-mortem human (n=22; age average: 41±17years, range: 6–71 years) and cynomolgus monkey (n=19; age average: 7.7±1.8 years, range: 4.2–10 years) tissues including the lens, capsule, zonules, ciliary body, and sclera were mounted in an optomechanical lens stretching system. Starting at zero load, the sclera was symmetrically stretched to 2mm in 0.25 steps at a speed of 0.1mm.s−1. The load and lens diameter were measured at each step. The lens contents were removed through a mini-capsulorhexis. The stretching cycles were repeated on the empty capsular bag. The forces required to stretch the natural lens and empty bag were quantified as a function of age and compared. Results The force required to stretch the empty lens capsule was independent of age (human=2.6–34.9g/mm [25.2–342.7mN/mm], monkey=8.2–21.3g/mm [80.3–208.6mN/mm]). The ratio of the force required to stretch the empty lens capsule to the force required to stretch the natural lens decreases with age in human and monkey lenses (p=0.003, p=0.72, respectively). Conclusions The mechanical properties of the empty lens capsule assessed ex vivo in a lens stretcher remain constant with age, suggesting that the changes in elasticity of the lens capsule do not play a significant role in presbyopia. In young eyes, the lens capsule determines the force required to stretch the whole lens. The age-related increase in force required to stretch the lens is due to changes in the lens contents. PMID:18515568

  8. Methionine Sulfoxide Reductases B1, B2, and B3 Are Present in the Human Lens and Confer Oxidative Stress Resistance to Lens Cells

    PubMed Central

    Marchetti, Maria A.; Pizarro, Gresin O.; Sagher, Daphna; DeAmicis, Candida; Brot, Nathan; Hejtmancik, J. Fielding; Weissbach, Herbert; Kantorow, Marc

    2005-01-01

    Purpose Methionine-sulfoxide reductases are unique, in that their ability to repair oxidized proteins and MsrA, which reduces S-methionine sulfoxide, can protect lens cells against oxidative stress damage. To date, the roles of MsrB1, -B2 and -B3 which reduce R-methionine sulfoxide have not been established for any mammalian system. The present study was undertaken to identify those MsrBs expressed by the lens and to evaluate the enzyme activities, expression patterns, and abilities of the identified genes to defend lens cells against oxidative stress damage. Methods Enzyme activities were determined with bovine lens extracts. The identities and spatial expression patterns of MsrB1, -B2, and -B3 transcripts were examined by RT-PCR in human lens and 21 other tissues. Oxidative stress resistance was measured using short interfering (si)RNA–mediated gene-silencing in conjunction with exposure to tert-butyl hydroperoxide (tBHP) and MTS viability measurements in SRA04/01 human lens epithelial cells. Results. Forty percent of the Msr enzyme activity present in the lens was MsrB, whereas the remaining enzyme activity was MsrA. MsrB1 (selenoprotein R, localized in the cytosol and nucleus), MsrB2 (CBS-1, localized in the mitochondria), and MsrB3 (localized in the endoplasmic reticulum and mitochondria) were all expressed by the lens. These genes exhibit asymmetric expression patterns between different human tissues and different lens sublocations, including lens fibers. All three genes are required for lens cell viability, and their silencing in lens cells results in increased oxidative-stress–induced cell death. Conclusions. The present data suggest important roles for both MsrA and -Bs in lens cell viability and oxidative stress protection. The differential tissue distribution and lens expression patterns of these genes, coupled with increased oxidative-stress–induced cell death on their deletion provides evidence that they are important for lens cell function

  9. Skin mirrors human aging.

    PubMed

    Nikolakis, Georgios; Makrantonaki, Evgenia; Zouboulis, Christos C

    2013-12-01

    Abstract Aged skin exhibits disturbed lipid barrier, angiogenesis, production of sweat, immune functions, and calcitriol synthesis as well as the tendency towards development of certain benign or malignant diseases. These complex biological processes comprise endogenous and exogenous factors. Ethnicity also markedly influences the phenotype of skin aging. The theories of cellular senescence, telomere shortening and decreased proliferative capacity, mitochondrial DNA single mutations, the inflammation theory, and the free radical theory try to explain the biological background of the global aging process, which is mirrored in the skin. The development of advanced glycation end-products and the declining hormonal levels are major factors influencing intrinsic aging. Chronic photodamage of the skin is the prime factor leading to extrinsic skin aging. The deterioration of important skin functions, due to intrinsic and extrinsic aging, leads to clinical manifestations, which mirror several internal age-associated diseases such as diabetes, arterial hypertension and malignancies.

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. LENS* 4: a program for calculation of geometric optics of the human eye

    SciTech Connect

    Doss, J.D.

    1982-10-01

    A computer program (LENS* 4) has been written that may be used for ray-trace calculations of human or animal eyes. The user enters all relevant eye specifications, and the program calculates ray segments from a (specified) external object. From the ray calculations, the program yields data on image location, image distance from the retina, retinal spot size, and effective pupil diameter. The program also allows entry of simple corrective lens systems that simulate a contact lens or ordinary spectacles. Graphics output illustrating the eye cross section, corrective lens, and rays is provided either on the CRT, thermal printer, or graphics plotter. Although the program is written in BASIC, many of the statements (particularly in the graphics section) are peculiar to the Hewlett-Packard 9845B desktop computer.

  15. 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.

  16. 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

  17. 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

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

    PubMed

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

    2016-08-01

    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

  19. Low-Cell-Number Epigenome Profiling Aids the Study of Lens Aging and Hematopoiesis.

    PubMed

    Zheng, Xiaobin; Yue, Sibiao; Chen, Haiyang; Weber, Blake; Jia, Junling; Zheng, Yixian

    2015-11-17

    Understanding how chromatin modification regulates development and disease can be limited by available material. Despite recent progress, balancing high-quality and reliable mapping using chromatin-immunoprecipitation-based deep sequencing (ChIP-seq) remains a challenge. We report two techniques, recovery via protection (RP)-ChIP-seq and favored amplification RP-ChIP-seq (FARP-ChIP-seq), that provide reproducible mapping in as few as 500 cells. RP-ChIP-seq allows detection of age-associated epigenetic changes in a single mouse lens, whereas FARP-ChIP-seq accurately maps histone H3 lysine 4 trimethylation (H3K4me3) and H3K27me3 in long-term hematopoietic stem cells (LT-HSCs), short-term HSCs (ST-HSCs), and multi-potent progenitors (MPPs) from one mouse. These datasets not only highlight genes that may be involved in lens aging but also indicate a lack of H3K4me3/H3K27me3 bivalency on hematopoietic genes in HSCs. PMID:26549448

  20. 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.

  1. 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.

  2. Effects of cadmium chloride on the cultured human lens epithelial cells

    PubMed Central

    Song, Nang-Hee

    2012-01-01

    Purpose To investigate cadmium chloride cytotoxicity in human lens epithelial cells as well as the mode of cell death and its mechanism. Methods Cultured human lens epithelial cells were challenged with cadmium chloride. Morphological changes of human lens epithelial cells caused by cadmium chloride exposure were evaluated by microscope. Cell viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-dipheny tetrazolium bromice (MTT) assay. To explore the mechanism of cell death, p53 and caspase-8 levels were measured by western blotting. Results Microscopic examination indicated that cell death increased after cadmium chloride exposure compared to untreated cells. The MTT assay demonstrated that cadmium chloride significantly decreased cell viability in a dose dependent way. Western blot and quantitative analysis showed that both p53 and caspase-8 increased after cell exposure to cadmium chloride. p53 increased 210% and caspase-8 increased 30% in the experimental group as compared with the control group. Conclusions Cadmium chloride induced cytotoxicity and apoptosis in human lens epithelial cells and the mechanism of apoptosis involve an increased expression of p53 and caspase-8. PMID:22550391

  3. 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…

  4. The origins of human ageing.

    PubMed Central

    Kirkwood, T B

    1997-01-01

    The origins of human ageing are to be found in the origins and evolution of senescence as a general feature in the life histories of higher animals. Ageing is an intriguing problem in evolutionary biology because a trait that limits the duration of life, including the fertile period, has a negative impact on Darwinian fitness. Current theory suggests that senescence occurs because the force of natural selection declines with age and because longevity is only acquired at some metabolic cost. In effect, organisms may trade late survival for enhanced reproductive investments in earlier life. The comparative study of ageing supports the general evolutionary theory and reveals that human senescence, while broadly similar to senescence in other mammalian species, has distinct features, such as menopause, that may derive from the interplay of biological and social evolution. PMID:9460059

  5. 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.

  6. 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. PMID:27500118

  7. 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

  8. Multimodal 3-D reconstruction of human anatomical structures using SurLens Visualization System.

    PubMed

    Adeshina, A M; Hashim, R; Khalid, N E A; Abidin, S Z Z

    2013-03-01

    In the medical diagnosis and treatment planning, radiologists and surgeons rely heavily on the slices produced by medical imaging devices. Unfortunately, these image scanners could only present the 3-D human anatomical structure in 2-D. Traditionally, this requires medical professional concerned to study and analyze the 2-D images based on their expert experience. This is tedious, time consuming and prone to error; expecially when certain features are occluding the desired region of interest. Reconstruction procedures was earlier proposed to handle such situation. However, 3-D reconstruction system requires high performance computation and longer processing time. Integrating efficient reconstruction system into clinical procedures involves high resulting cost. Previously, brain's blood vessels reconstruction with MRA was achieved using SurLens Visualization System. However, adapting such system to other image modalities, applicable to the entire human anatomical structures, would be a meaningful contribution towards achieving a resourceful system for medical diagnosis and disease therapy. This paper attempts to adapt SurLens to possible visualisation of abnormalities in human anatomical structures using CT and MR images. The study was evaluated with brain MR images from the department of Surgery, University of North Carolina, United States and CT abdominal pelvic, from the Swedish National Infrastructure for Computing. The MR images contain around 109 datasets each of T1-FLASH, T2-Weighted, DTI and T1-MPRAGE. Significantly, visualization of human anatomical structure was achieved without prior segmentation. SurLens was adapted to visualize and display abnormalities, such as an indication of walderstrom's macroglobulinemia, stroke and penetrating brain injury in the human brain using Magentic Resonance (MR) images. Moreover, possible abnormalities in abdominal pelvic was also visualized using Computed Tomography (CT) slices. The study shows SurLens' functionality as

  9. 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

  10. Effects of iron ions, protons and X rays on human lens cell differentiation.

    PubMed

    Chang, P Y; Bjornstad, K A; Rosen, C J; McNamara, M P; Mancini, R; Goldstein, L E; Chylack, L T; Blakely, E A

    2005-10-01

    We have investigated molecular changes in cultured differentiating human lens epithelial cells exposed to high-energy accelerated iron-ion beams as well as to protons and X rays. In this paper, we present results on the effects of radiation on gene families that include or are related to DNA damage, cell cycle regulators, cell adhesion molecules, and cell cytoskeletal function. A limited microarray survey with a panel of cell cycle-regulated genes illustrates that irradiation with protons altered the gene expression pattern of human lens epithelial cells. A focus of our work is CDKN1A (p21(CIP1/WAF1)), a protein that we demonstrate here has a role in several pathways functionally related to LET-responsive radiation damage. We quantitatively assessed RNA and protein expression in a time course before and after single 4-Gy radiation doses and demonstrated that transcription and translation of CDKN1A are both temporally regulated after exposure. Furthermore, we show qualitative differences in the distribution of CDKN1A immunofluorescence signals after exposure to X rays, protons or iron ions, suggesting that LET effects likely play a role in the misregulation of gene function in these cells. A model of molecular and cellular events is proposed to account for precataractous changes in the human lens after exposure to low- or high-LET radiations. PMID:16187763

  11. 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.

  12. 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.

  13. 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.

  14. 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. PMID:26974795

  15. 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

  16. Cataract-related changes in protein aggregates of human lens studied by ultracentrifugation.

    PubMed

    Twardowski, J; Hoja, D

    1990-01-01

    In human lens, cataract development causes an increase in the amount of protein aggregates. Their specific density of 1.25 g/ml is much higher than that of 1.14 g/ml and 1.06 g/ml obtained for water-soluble proteins. During the formation of water-insoluble aggregates their size varies up to some micrometers. Infrared spectra of water-soluble protein and in the aggregates confirm that the content of bound water in aggregates decreases. PMID:2279587

  17. Comprehensive Analysis of Maillard Protein Modifications in Human Lenses: Effect of Age and Cataract

    PubMed Central

    Smuda, Mareen; Henning, Christian; Raghavan, Cibin T.; Johar, Kaid; Vasavada, Abhay R.; Nagaraj, Ram H.; Glomb, Marcus A.

    2015-01-01

    In human lens proteins, advanced glycation endproducts (AGEs) originate from the reaction of glycating agents, e.g., vitamin C and glucose. AGEs have been considered to play a significant role in lens aging and cataract formation. Although several AGEs have been detected in the human lens, the contribution of individual glycating agents to their formation remains unclear. A highly sensitive liquid chromatography–tandem mass spectrometry multimethod was developed that allowed us to quantitate 21 protein modifications in normal and cataractous lenses, respectively. N6-Carboxymethyl lysine, N6-carboxyethyl lysine, N7-carboxyethyl arginine, methylglyoxal hydroimidazolone 1, and N6-lactoyl lysine were found to be the major Maillard protein modifications among these AGEs. The novel vitamin C specific amide AGEs, N6-xylonyl and N6-lyxonyl lysine, but also AGEs from glyoxal were detected, albeit in minor quantities. Among the 21 modifications, AGEs from the Amadori product (derived from the reaction of glucose and lysine) and methylglyoxal were dominant. PMID:25849437

  18. 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.

  19. In Vivo Measurement of Age-Related Stiffening in the Crystalline Lens by Brillouin Optical Microscopy

    PubMed Central

    Scarcelli, Giuliano; Kim, Pilhan; Yun, Seok Hyun

    2011-01-01

    Abtract The biophysical and biomechanical properties of the crystalline lens (e.g., viscoelasticity) have long been implicated in accommodation and vision problems, such as presbyopia and cataracts. However, it has been difficult to measure such parameters noninvasively. Here, we used in vivo Brillouin optical microscopy to characterize material acoustic properties at GHz frequency and measure the longitudinal elastic moduli of lenses. We obtained three-dimensional elasticity maps of the lenses in live mice, which showed biomechanical heterogeneity in the cortex and nucleus of the lens with high spatial resolution. An in vivo longitudinal study of mice over a period of 2 months revealed a marked age-related stiffening of the lens nucleus. We found remarkably good correlation (log-log linear) between the Brillouin elastic modulus and the Young's modulus measured by conventional mechanical techniques at low frequencies (∼1 Hz). Our results suggest that Brillouin microscopy is potentially useful for basic and animal research and clinical ophthalmology. PMID:21943436

  20. [Aging of the human testis].

    PubMed

    Sibert, Louis; Lacarrière, Emeric; Safsaf, Athmane; Rives, Nathalie

    2014-02-01

    The morphological and histological changes related to testicular aging are: volume decrease, arteriolar sclerosis, degeneration of Leydig cells and Sertoli, depletion of germ cells and thickening of the tunica albuginea testis. The participation in testicular androgen decline in aging is related to the decrease in the number of Leydig cells associated with alterations in the functioning of the hypothalamic-pituitary axis Sperm volume, concentration and total number, motility and morphology of sperm decrease with aging male. The interindividual variability of sperm parameters, the variability of methodologies for data collection and selection of patients must be careful in interpreting the published results. Overall, the quality of sperm decreases progressively with age, without any age limit that can be individualized. Alterations of spermatogenesis do not seem significantly compromising fertility in the elderly. The clinical impact of testicular aging implies androgen production decrease and diseases associated with aging.

  1. [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.

  2. [Experimental models of human skin aging].

    PubMed

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

    2016-02-01

    The skin is a representative model for the study of human aging. Despite the high regenerative capacity of the skin, skin physiology changes over the course of life. Medical and cosmetic research is trying to prevent aging, to slow, to stop, or to reverse it. Effects of age-related DNA damage and of changing skin structure on pharmacological parameters are largely unknown. This review article summarizes the state of scientific knowledge in the field of experimental models of human skin aging and shows approaches to improve organotypic skin models, to develop predictive models of aging, and improve aging research. PMID:26743051

  3. 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

  4. 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.

  5. 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. PMID:27339748

  6. Genotype × age interaction in human transcriptional ageing

    PubMed Central

    Kent, Jack W.; Göring, Harald H. H.; Charlesworth, Jac C.; Drigalenko, Eugene; Diego, Vincent P.; Curran, Joanne E.; Johnson, Matthew P.; Dyer, Thomas D.; Cole, Shelley A.; Jowett, Jeremy B. M.; Mahaney, Michael C.; Comuzzie, Anthony G.; Almasy, Laura; Moses, Eric K.; Blangero, John; Williams-Blangero, Sarah

    2012-01-01

    Individual differences in biological ageing (i.e., the rate of physiological response to the passage of time) may be due in part to genotype-specific variation in gene action. However, the sources of heritable variation in human age-related gene expression profiles are largely unknown. We have profiled genome-wide expression in peripheral blood mononuclear cells from 1,240 individuals in large families and found 4,472 human autosomal transcripts, representing ~4,349 genes, significantly correlated with age. We identified 623 transcripts that show genotype by age interaction in addition to a main effect of age, defining a large set of novel candidates for characterization of the mechanisms of differential biological ageing. We applied a novel SNP genotype×age interaction test to one of these candidates, the ubiquilin-like gene UBQLNL, and found evidence of joint cis-association and genotype by age interaction as well as trans-genotype by age interaction for UBQLNL expression. Both UBQLNL expression levels at recruitment and cis genotype are associated with longitudinal cancer risk in our study cohort. PMID:22871458

  7. Dose rates to the human lens from a SR-90 applicator modeled with Monte Carlo computer techniques

    SciTech Connect

    Silberstein, E.B.; Gleckler, M.; Valentine, J.

    1995-05-01

    Strontium-90 (beta-emitting) applicators for the treatment of pterygia carry the potential for significant (possibly cataractogenic) lens doses previously calculated with imprecise or inaccurate assumptions. We sought to apply modern dosimetry techniques to this problem using the Monte Carlo computer code MCNP version 4.A to model the human eye irradiated with a commonly employed Sr-90 applicator. The code was configured to compute dose rate to any part of the eye, focusing on those tissues (sclera, lens) directly under the applicator. The model was validated by calculating the surface dose delivered by the applicator to the sclera from MCNP results and comparing this to the manufacturer specified value of this parameter. The scleral surface dose rate from a 1.85 GBq (50 mCi) Sr-90 source was 60.5 cGy/sec, with an average dose rate to the underlying sclera about 42 cGy/sec. In the surface region of the lends under the 1.85 GBq Sr-90 applicator, with depth 0.5 m width 1.5 mm over a 90{degrees} arc tangential to the applicator, the dose rate was 6.6 cGy/min, and in the next underlying region of the lens with 0.5 mm thickness 4.3 cGy/min. Isodose curves have been calculated for the lens and entire eye. Our computer program permits calibration of Sr-90 applicators and provides accurate dosimetry from these applicators to the sclera and all regions of the lens. A total lens dose is meaningless. The periphery of the lens will receive cataractogenic doses when a commonly employed dose (20 Gy) for pterygium treatment is used.

  8. Melatonin and human skin aging

    PubMed Central

    Kleszczynski, Konrad; Fischer, Tobias W.

    2012-01-01

    Like the whole organism, skin follows the process of aging during life-time. Additional to internal factors, several environmental factors, such as solar radiation, considerably contribute to this process. While fundamental mechanisms regarding skin aging are known, new aspects of anti-aging agents such as melatonin are introduced. Melatonin is a hormone produced in the glandula pinealis that follows a circadian light-dependent rhythm of secretion. It has been experimentally implicated in skin functions such as hair cycling and fur pigmentation, and melatonin receptors are expressed in many skin cell types including normal and malignant keratinocytes, melanocytes and fibroblasts. It possesses a wide range of endocrine properties as well as strong antioxidative activity. Regarding UV-induced solar damage, melatonin distinctly counteracts massive generation of reactive oxygen species, mitochondrial and DNA damage. Thus, there is considerable evidence for melatonin to be an effective anti-skin aging compound, and its various properties in this context are described in this review. PMID:23467217

  9. 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)

  10. Age-dependent variation of the Gradient Index profile in human crystalline lenses.

    PubMed

    de Castro, A; Siedlecki, D; Borja, David; Uhlhorn, Stephen; Parel, Jean-Marie; Manns, Fabrice; Marcos, S

    2011-01-01

    PURPOSE: To reconstruct the gradient index (GRIN) profile of human crystalline lenses ex-vivo using Optical Coherence Tomography (OCT) imaging with an optimization technique and to study the dependence of the GRIN profile with age. METHODS: Cross-sectional images of nine isolated human crystalline lenses with ages ranging from 6 to 72 (post mortem time 1 to 4 days) were obtained using a custom-made OCT system. Lenses were extracted from whole cadaver globes and placed in a measurement chamber filled with preservation medium (DMEM). Lenses were imaged with the anterior surface up and then flipped over and imaged again, to obtain posterior lens surface profiles both undistorted and distorted by the refraction through the anterior crystalline lens and GRIN. The GRIN distribution of the lens was described with three variables by means of power function, with variables being the nucleus and surface index, and a power coefficient that describes the decay of the refractive index from the nucleus to the surface. An optimization method was used to search for the parameters that produced the best match of the distorted posterior surface. RESULTS: The distorted surface was simulated with accuracy around the resolution of the OCT system (under 15 µm). The reconstructed refractive index values ranged from 1.356 to 1.388 for the surface, and from 1.396 to 1.434 for the nucleus. The power coefficient ranged between 3 and 18. The power coefficient increased significantly with age, at a rate of 0.24 per year. CONCLUSION: Optical Coherence Tomography allowed optical, non-invasive measurement of the 2-D gradient index profile of the isolated human crystalline lens ex vivo. The age-dependent variation of the changes is consistent with previous data using magnetic resonance imaging, and the progressive formation of a refractive index plateau. PMID:22865954

  11. Age-dependent variation of the Gradient Index profile in human crystalline lenses

    PubMed Central

    de Castro, A.; Siedlecki, D.; Borja, David; Uhlhorn, Stephen; Parel, Jean-Marie; Manns, Fabrice; Marcos, S.

    2011-01-01

    Purpose To reconstruct the gradient index (GRIN) profile of human crystalline lenses ex-vivo using Optical Coherence Tomography (OCT) imaging with an optimization technique and to study the dependence of the GRIN profile with age. Methods Cross-sectional images of nine isolated human crystalline lenses with ages ranging from 6 to 72 (post mortem time 1 to 4 days) were obtained using a custom-made OCT system. Lenses were extracted from whole cadaver globes and placed in a measurement chamber filled with preservation medium (DMEM). Lenses were imaged with the anterior surface up and then flipped over and imaged again, to obtain posterior lens surface profiles both undistorted and distorted by the refraction through the anterior crystalline lens and GRIN. The GRIN distribution of the lens was described with three variables by means of power function, with variables being the nucleus and surface index, and a power coefficient that describes the decay of the refractive index from the nucleus to the surface. An optimization method was used to search for the parameters that produced the best match of the distorted posterior surface. Results The distorted surface was simulated with accuracy around the resolution of the OCT system (under 15 µm). The reconstructed refractive index values ranged from 1.356 to 1.388 for the surface, and from 1.396 to 1.434 for the nucleus. The power coefficient ranged between 3 and 18. The power coefficient increased significantly with age, at a rate of 0.24 per year. Conclusion Optical Coherence Tomography allowed optical, non-invasive measurement of the 2-D gradient index profile of the isolated human crystalline lens ex vivo. The age-dependent variation of the changes is consistent with previous data using magnetic resonance imaging, and the progressive formation of a refractive index plateau. PMID:22865954

  12. Age-dependent variation of the gradient index profile in human crystalline lenses

    NASA Astrophysics Data System (ADS)

    de Castro, Alberto; Siedlecki, Damian; Borja, David; Uhlhorn, Stephen; Parel, Jean-Marie; Manns, Fabrice; Marcos, Susana

    2011-11-01

    An investigation was carried out with the aim of reconstructing the gradient index (GRIN) profile of human crystalline lenses ex-vivo using optical coherence tomography (OCT) imaging with an optimization technique and to study the dependence of the GRIN profile with age. Cross-sectional images of nine isolated human crystalline lenses with ages ranging from 6 to 72 (post-mortem time 1 to 4 days) were obtained using a custom-made OCT system. Lenses were extracted from whole cadaver globes and placed in a measurement chamber filled with preservation medium (DMEM). Lenses were imaged with the anterior surface up and then flipped over and imaged again, to obtain posterior lens surface profiles both undistorted and distorted by the refraction through the anterior crystalline lens and GRIN. The GRIN distribution of the lens was described with three variables by means of power function, with variables being the nucleus and surface index, and a power coefficient that describes the decay of the refractive index from the nucleus to the surface. An optimization method was used to search for the parameters that produced the best match of the distorted posterior surface. The distorted surface was simulated with accuracy around the resolution of the OCT system (under 15 µm). The reconstructed refractive index values ranged from 1.356 to 1.388 for the surface, and from 1.396 to 1.434 for the nucleus. The power coefficient ranged between 3 and 18. The power coefficient increased significantly with age, at a rate of 0.24 per year. Optical coherence tomography allowed optical, non-invasive measurement of the 2D gradient index profile of the isolated human crystalline lens ex vivo. The age-dependent variation of the changes is consistent with previous data using magnetic resonance imaging, and the progressive formation of a refractive index plateau.

  13. 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.

  14. Distribution of pseudoexfoliation material on anterior segment structures in human autopsy eyes after cataract surgery with intraocular lens implantation.

    PubMed

    Schmack, Ingo; Auffarth, Gerd Uwe

    2016-06-01

    The purpose of the study was to evaluate the distribution and amount of pseudoexfoliation material (PXM) on anterior segment structures in pseudophakic human autopsy eyes with pseudoexfoliation (PEX) syndrome and to study its impact on fixation and decentration of posterior chamber intraocular lenses (IOLs). Sixteen human autopsy eyes (donor age [mean ± SD] 77.5 ± 8.6 years; range, 70-90 years) with history of cataract surgery and PEX syndrome were analyzed for distribution and accumulation of PXM on structures of the anterior segment by light microscopy. Quantitative IOL decentration measurements were performed using the Miyake-Apple posterior view technique. All 16 eyes displayed IOLs which were either fixed symmetrically in the capsular bag (n = 8) or asymmetrically with one haptic in the sulcus and one in the bag (n = 7) or at the pars plicata of the ciliary body (n = 1). In the majority, PXM was found around the pars plicata (average grade: 1.6 ± 0.53 µm) and the lens capsule (average grade: 1.05 ± 0.46 µm). Minor amounts were detected at the pars plana and the trabecular meshwork. IOL decentration measurements ranged from 0.51 ± 0.35 (symmetrical-fixation) to 0.61 ± 0.43 mm (asymmetrical-fixation). There was only a weak statistically not significant correlation in regard to the amount of PXM and IOL decentration and between PXM distribution and the IOL fixation site. PXM contributes to weakening of the suspensory apparatus of the crystalline lens. Although PXM induced tissue alterations predispose for a broad spectrum of intra- and postoperative complications, the amount and distribution of PXM on different anterior segment structures showed only a weak correlation to IOL decentration or fixation location. PMID:26307751

  15. Invited review: aging and human temperature regulation.

    PubMed

    Kenney, W Larry; Munce, Thayne A

    2003-12-01

    This mini-review focuses on the effects of aging on human temperature regulation. Although comprehensive reviews have been published on this topic (Kenney WL. Exercise and Sport Sciences Reviews, Baltimore: Williams & Wilkins, 1997, p. 41-76; Pandolf KB. Exp Aging Res 17: 189-204, 1991; Van Someren EJ, Raymann RJ, Scherder EJ, Daanen HA, and Swaab DF. Ageing Res Rev 1: 721-778, 2002; and Young AJ. Exp Aging Res 17: 205-213, 1991), this mini-review concisely summarizes the present state of knowledge about human temperature regulation and aging in thermoneutral conditions, as well as during hypo- and hyperthermic challenges. First, we discuss age-related effects on baseline body core temperature and phasing rhythms of the circadian temperature cycle. We then examine the altered physiological responses to cold stress that result from aging, including attenuated peripheral vasoconstriction and reduced cold-induced metabolic heat production. Finally, we present the age-related changes in sweating and cardiovascular function associated with heat stress. Although epidemiological evidence of increased mortality among older adults from hypo- and hyperthermia exists, this outcome does not reflect an inability to thermoregulate with advanced age. In fact, studies that have attempted to separate the effects of chronological age from concurrent factors, such as fitness level, body composition, and the effects of chronic disease, have shown that thermal tolerance appears to be minimally compromised by age.

  16. The mechanical response of the porcine lens to a spinning test.

    PubMed

    Reilly, Matthew A; Martius, Philipp; Kumar, Saurav; Burd, Harvey J; Stachs, Oliver

    2016-06-01

    The pig lens has been used as a model for presbyopia as pigs lack accommodative ability. Previous studies using microindentation have indicated that the shear modulus distribution is qualitatively similar to that of the aged human lens and that the lens does not alter its refractive power due to equatorial stretching. A lens spinning test was used to determine whether prior lens stiffness data obtained from a sectioned porcine lens were reliable and whether the testing conditions significantly influence the lens' mechanical properties. The elastic modulus distribution determined for fresh lenses closely matched that measured previously using a microindentation test. Confocal scanning laser microscopy was used to evaluate changes to the lens' structure arising from mechanical stress and following storage for up to one week.

  17. Oncogenic Human Papillomaviruses Activate the Tumor-Associated Lens Epithelial-Derived Growth Factor (LEDGF) Gene

    PubMed Central

    Leitz, Jenny; Reuschenbach, Miriam; Lohrey, Claudia; Honegger, Anja; Accardi, Rosita; Tommasino, Massimo; Llano, Manuel; von Knebel Doeberitz, Magnus; Hoppe-Seyler, Karin; Hoppe-Seyler, Felix

    2014-01-01

    The expression of the human papillomavirus (HPV) E6/E7 oncogenes is crucial for HPV-induced malignant cell transformation. The identification of cellular targets attacked by the HPV oncogenes is critical for our understanding of the molecular mechanisms of HPV-associated carcinogenesis and may open novel therapeutic opportunities. Here, we identify the Lens Epithelial-Derived Growth Factor (LEDGF) gene as a novel cellular target gene for the HPV oncogenes. Elevated LEDGF expression has been recently linked to human carcinogenesis and can protect tumor cells towards different forms of cellular stress. We show that intracellular LEDGF mRNA and protein levels in HPV-positive cancer cells are critically dependent on the maintenance of viral oncogene expression. Ectopic E6/E7 expression stimulates LEDGF transcription in primary keratinocytes, at least in part via activation of the LEDGF promoter. Repression of endogenous LEDGF expression by RNA interference results in an increased sensitivity of HPV-positive cancer cells towards genotoxic agents. Immunohistochemical analyses of cervical tissue specimens reveal a highly significant increase of LEDGF protein levels in HPV-positive lesions compared to histologically normal cervical epithelium. Taken together, these results indicate that the E6/E7-dependent maintenance of intracellular LEDGF expression is critical for protecting HPV-positive cancer cells against various forms of cellular stress, including DNA damage. This could support tumor cell survival and contribute to the therapeutic resistance of cervical cancers towards genotoxic treatment strategies in the clinic. PMID:24604027

  18. Oncogenic human papillomaviruses activate the tumor-associated lens epithelial-derived growth factor (LEDGF) gene.

    PubMed

    Leitz, Jenny; Reuschenbach, Miriam; Lohrey, Claudia; Honegger, Anja; Accardi, Rosita; Tommasino, Massimo; Llano, Manuel; von Knebel Doeberitz, Magnus; Hoppe-Seyler, Karin; Hoppe-Seyler, Felix

    2014-03-01

    The expression of the human papillomavirus (HPV) E6/E7 oncogenes is crucial for HPV-induced malignant cell transformation. The identification of cellular targets attacked by the HPV oncogenes is critical for our understanding of the molecular mechanisms of HPV-associated carcinogenesis and may open novel therapeutic opportunities. Here, we identify the Lens Epithelial-Derived Growth Factor (LEDGF) gene as a novel cellular target gene for the HPV oncogenes. Elevated LEDGF expression has been recently linked to human carcinogenesis and can protect tumor cells towards different forms of cellular stress. We show that intracellular LEDGF mRNA and protein levels in HPV-positive cancer cells are critically dependent on the maintenance of viral oncogene expression. Ectopic E6/E7 expression stimulates LEDGF transcription in primary keratinocytes, at least in part via activation of the LEDGF promoter. Repression of endogenous LEDGF expression by RNA interference results in an increased sensitivity of HPV-positive cancer cells towards genotoxic agents. Immunohistochemical analyses of cervical tissue specimens reveal a highly significant increase of LEDGF protein levels in HPV-positive lesions compared to histologically normal cervical epithelium. Taken together, these results indicate that the E6/E7-dependent maintenance of intracellular LEDGF expression is critical for protecting HPV-positive cancer cells against various forms of cellular stress, including DNA damage. This could support tumor cell survival and contribute to the therapeutic resistance of cervical cancers towards genotoxic treatment strategies in the clinic.

  19. Derivation of Multiple Cranial Tissues and Isolation of Lens Epithelium-Like Cells From Human Embryonic Stem Cells

    PubMed Central

    2013-01-01

    Human embryonic stem cells (hESCs) provide a powerful tool to investigate early events occurring during human embryonic development. In the present study, we induced differentiation of hESCs in conditions that allowed formation of neural and non-neural ectoderm and to a lesser extent mesoderm. These tissues are required for correct specification of the neural plate border, an early embryonic transient structure from which neural crest cells (NCs) and cranial placodes (CPs) originate. Although isolation of CP derivatives from hESCs has not been previously reported, isolation of hESC-derived NC-like cells has been already described. We performed a more detailed analysis of fluorescence-activated cell sorting (FACS)-purified cell populations using the surface antigens previously used to select hESC-derived NC-like cells, p75 and HNK-1, and uncovered their heterogeneous nature. In addition to the NC component, we identified a neural component within these populations using known surface markers, such as CD15 and FORSE1. We have further exploited this information to facilitate the isolation and purification by FACS of a CP derivative, the lens, from differentiating hESCs. Two surface markers expressed on lens cells, c-Met/HGFR and CD44, were used for positive selection of multiple populations with a simultaneous subtraction of the neural/NC component mediated by p75, HNK-1, and CD15. In particular, the c-Met/HGFR allowed early isolation of proliferative lens epithelium-like cells capable of forming lentoid bodies. Isolation of hESC-derived lens cells represents an important step toward the understanding of human lens development and regeneration and the devising of future therapeutic applications. PMID:23341438

  20. Age peculiarities of human motor control in aging.

    PubMed

    Mankovsky, N B; Mints, A Y; Lisenyuk, V P

    1982-01-01

    A clinicophysiological investigation of motor control was carried out in 199 apparently healthy, socially active elderly (aged 60-69 years) and long-living (90 years and over) subjects in order to establish the peculiarities of the motor sphere specific to age-related changes of the nervous system. Analyzing the experimentally induced state of readiness (intention) before a spontaneous movement, we found an increase with age in the latent period of the muscle intentional activity (IA) parallel to an increase in the latent period of the spontaneous movement, a decrease in IA amplitude with more frequent structural deviations of the EMG in the prestarting period and a reduction of the required IA selectiveness. The described changes in the organization of readiness for a spontaneous movement seemed to be related with age impairment of supraspinal (mainly corticospinal) influences and may be used for an explanation of a number of clinical peculiarities of human motor control in late ontogenesis.

  1. Similarity of the yellow chromophores isolated from human cataracts with those from ascorbic acid-modified calf lens proteins: evidence for ascorbic acid glycation during cataract formation.

    PubMed

    Cheng, R; Lin, B; Lee, K W; Ortwerth, B J

    2001-07-27

    Chromatographic evidence supporting the similarity of the yellow chromophores isolated from aged human and brunescent cataract lenses and calf lens proteins ascorbylated in vitro is presented. The water-insoluble fraction from early stage brunescent cataract lenses was solubilized by sonication (WISS) and digested with a battery of proteolytic enzymes under argon to prevent oxidation. Also, calf lens proteins were incubated with ascorbic acid for 4 weeks in air and submitted to the same digestion. The percent hydrolysis of the proteins to amino acids was approximately 90% in every case. The content of yellow chromophores was 90, 130 and 250 A(330) units/g protein for normal human WISS, cataract WISS and ascorbate-modified bovine lens proteins respectively. Aliquots equivalent to 2.0 g of digested protein were subjected to size-exclusion chromatography on a Bio-Gel P-2 column. Six peaks were obtained for both preparations and pooled. Side by side thin-layer chromatography (TLC) of each peak showed very similar R(f) values for the long wavelength-absorbing fluorophores. Glycation with [U-(14)C]ascorbic acid, followed by digestion and Bio-Gel P-2 chromatography, showed that the incorporated radioactivity co-eluted with the A(330)-absorbing peaks, and that most of the fluorescent bands were labeled after TLC. Peaks 2 and 3 from the P-2 were further fractionated by preparative Prodigy C-18 reversed-phase high-performance liquid chromatography. Two major A(330)-absorbing peaks were seen in peak 2 isolated from human cataract lenses and 5 peaks in fraction 3, all of which eluted at the same retention times as those from ascorbic acid glycated calf lens proteins. HPLC fractionation of P-2 peaks 4, 5 and 6 showed many A(330)-absorbing peaks from the cataract WISS, only some of which were identical to the asorbylated proteins. The major fluorophores, however, were present in both preparations. These data provide new evidence to support the hypothesis that the yellow

  2. [(-)-Epigallocatechin gallate regulates expression of apoptotic genes and protects cultured human lens epithelial cells under hyperglycemia].

    PubMed

    Ye, Panpan; Lin, Kana; Li, Zhaochun; Liu, Jian; Yao, Ke; Xu, Wen

    2013-01-01

    (-)-Epigallocatechin gallate (EGCG), the most abundant component in green tea, has a potent anti-apoptotic activity. The purpose of this study was to investigate the protective effects of EGCG and their molecular mechanisms on high glucose-induced apoptosis of human lens epithelial cells (HLEB-3). HLEB-3 cells were exposed to various concentrations of glucose and EGCG. Cell death was assessed by MTT assay and flow cytometry using annexin V and propidium iodide. The expression of the Bcl-2 family, c-fos, c-myc and p53 was measured by real-time PCR. EGCG decreased the Bcl-2/Bax expression stimulated by a high glucose. Moreover, EGCG suppressed the high glucose-induced expression of c-fos, c-myc and p53. These findings suggest that EGCG protects HLEB-3 cells from high glucose-induced apoptosis by regulating the gene expression of the Bcl-2 family, c-fos, c-myc and p53. Thus, EGCG may have a potential protective effect against diabetic cataract formation.

  3. [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

  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. Fs-laser induced flexibility increase in the crystalline lens

    NASA Astrophysics Data System (ADS)

    Schumacher, S.; Fromm, M.; Lakharia, R.; Schaefer, M.; Oberheide, U.; Ripken, T.; Breitenfeld, P.; Gerten, G.; Ertmer, W.; Lubatschowksi, H.

    2007-02-01

    Presbyopia is one age related effect every human is suffering beginning at the age of about 45 years. Reading glasses are the conventional treatment so far. According to the Helmholtz theory the loss of accommodation in age is due to the hardening and the resulting loss of elasticity of the crystalline lens. However the ciliary muscle and the lens capsule stay active, respectively. Therefore a possible treatment concept is to regain the flexibility by inducing gliding planes in form of microcuts inside the lens. The increase of flexibility in young porcine lenses by different cutting patterns was shown by Ripken et al. 1, 2 who verified the increase in flexibility by the spinning test introduced by Fisher. 3 We will present our first measurements of flexibility increase of human donor lenses. Furthermore the influence of the laser cuts into the lens on the accommodation amplitude will be shown in a three dimensional finite-element simulation.

  6. Targeted deletion of the murine Lgr4 gene decreases lens epithelial cell resistance to oxidative stress and induces age-related cataract formation.

    PubMed

    Zhu, Jun; Hou, Qiang; Dong, Xiang Da; Wang, Zhenlian; Chen, Xiaoyan; Zheng, Dandan; Zhou, Linglin; He, Chao; Liu, Mingyao; Tu, LiLi; Qu, Jia

    2015-01-01

    Oxidative stress contributes to the formation of cataracts. The leucine rich repeat containing G protein-coupled receptor 4 (LGR4, also known as GPR48), is important in many developmental processes. Since deletion of Lgr4 has previously been shown to lead to cataract formation in mice, we sought to determine the specific role that Lgr4 plays in the formation of cataracts. Initially, the lens opacities of Lgr4(-/-) mice at different ages without ocular anterior segment dysgenesis (ASD) were evaluated with slit-lamp biomicroscopy. Lenses from both Lgr4(-/-) and wild-type mice were subjected to oxidation induced protein denaturation to assess the ability of the lens to withstand oxidation. The expression of antioxidant enzymes was evaluated with real-time quantitative PCR. Phenotypically, Lgr4(-/-) mice showed earlier onset of lens opacification and higher incidence of cataract formation compared with wild-type mice of similar age. In addition, Lgr4(-/-) mice demonstrated increased sensitivity to environmental oxidative damage, as evidenced by altered protein expression. Real-time quantitative PCR showed that two prominent antioxidant defense enzymes, catalase (CAT) and superoxidase dismutase-1 (SOD1), were significantly decreased in the lens epithelial cells of Lgr4(-/-) mice. Our results suggest that the deletion of Lgr4 can lead to premature cataract formation, as well as progressive deterioration with aging. Oxidative stress and altered expression of several antioxidant defense enzymes contribute to the formation of cataracts. PMID:25811370

  7. Stiffening of Human Skin Fibroblasts with Age

    PubMed Central

    Schulze, Christian; Wetzel, Franziska; Kueper, Thomas; Malsen, Anke; Muhr, Gesa; Jaspers, Soeren; Blatt, Thomas; Wittern, Klaus-Peter; Wenck, Horst; Käs, Josef A.

    2010-01-01

    Changes in mechanical properties are an essential characteristic of the aging process of human skin. Previous studies attribute these changes predominantly to the altered collagen and elastin organization and density of the extracellular matrix. Here, we show that individual dermal fibroblasts also exhibit a significant increase in stiffness during aging in vivo. With the laser-based optical cell stretcher we examined the viscoelastic biomechanics of dermal fibroblasts isolated from 14 human donors aged 27 to 80. Increasing age was clearly accompanied by a stiffening of the investigated cells. We found that fibroblasts from old donors exhibited an increase in rigidity of ∼60% with respect to cells of the youngest donors. A FACS analysis of the content of the cytoskeletal polymers shows a shift from monomeric G-actin to polymerized, filamentous F-actin, but no significant changes in the vimentin and microtubule content. The rheological analysis of fibroblast-populated collagen gels demonstrates that cell stiffening directly results in altered viscoelastic properties of the collagen matrix. These results identify a new mechanism that may contribute to the age-related impairment of elastic properties in human skin. The altered mechanical behavior might influence cell functions involving the cytoskeleton, such as contractility, motility, and proliferation, which are essential for reorganization of the extracellular matrix. PMID:20959083

  8. Identification of Kynoxazine, a Novel Fluorescent Product of the Reaction between 3-Hydroxykynurenine and Erythrulose in the Human Lens, and Its Role in Protein Modification.

    PubMed

    Rakete, Stefan; Nagaraj, Ram H

    2016-04-29

    Kynurenine pathway metabolites and ascorbate degradation products are present in human lenses. In this study, we showed that erythrulose, a major ascorbate degradation product, reacts spontaneously with 3-hydroxykynurenine to form a fluorescent product. Structural characterization of the product revealed it to be 2-amino-4-(2-hydroxy-3-(2-hydroxyethyl)-2H-benzo[b][1,4]oxazin-5-yl)-4-oxobutanoic acid, which we named kynoxazine. Unlike 3-hydroxykynurenine, 3-hydroxykynurenine glucoside and kynurenine were unable to form a kynoxazine-like compound, which suggested that the aminophenol moiety in 3-hydroxykynurenine is essential for the formation of kynoxazine. This reasoning was confirmed using a model compound, 1-(2-amino-3-hydroxyphenyl)ethan-1-one, which is an aminophenol lacking the amino acid moiety of 3-hydroxykynurenine. Ultra-performance liquid chromatography-tandem mass spectrometry analyses showed that kynoxazine is present in the human lens at levels ranging from 0 to 64 pmol/mg lens. Kynoxazine as well as erythrulose degraded under physiological conditions to generate 3-deoxythreosone, which modified and cross-linked proteins through the formation of an arginine adduct, 3-deoxythreosone-derived hydroimidazolone, and a lysine-arginine cross-linking adduct, 3-deoxythreosone-derived hydroimidazolimine cross-link. Ultra-performance liquid chromatography-tandem mass spectrometry quantification showed that 32-169 pmol/mg protein of 3-deoxythreosone-derived hydroimidazolone and 1.1-11.2 pmol/mg protein of 3-deoxythreosone-derived hydroimidazolimine cross-link occurred in aging lenses. Taken together, these results demonstrate a novel biochemical mechanism by which ascorbate oxidation and the kynurenine pathway intertwine, which could promote protein modification and cross-linking in aging human lenses.

  9. Identification of Kynoxazine, a Novel Fluorescent Product of the Reaction between 3-Hydroxykynurenine and Erythrulose in the Human Lens, and Its Role in Protein Modification.

    PubMed

    Rakete, Stefan; Nagaraj, Ram H

    2016-04-29

    Kynurenine pathway metabolites and ascorbate degradation products are present in human lenses. In this study, we showed that erythrulose, a major ascorbate degradation product, reacts spontaneously with 3-hydroxykynurenine to form a fluorescent product. Structural characterization of the product revealed it to be 2-amino-4-(2-hydroxy-3-(2-hydroxyethyl)-2H-benzo[b][1,4]oxazin-5-yl)-4-oxobutanoic acid, which we named kynoxazine. Unlike 3-hydroxykynurenine, 3-hydroxykynurenine glucoside and kynurenine were unable to form a kynoxazine-like compound, which suggested that the aminophenol moiety in 3-hydroxykynurenine is essential for the formation of kynoxazine. This reasoning was confirmed using a model compound, 1-(2-amino-3-hydroxyphenyl)ethan-1-one, which is an aminophenol lacking the amino acid moiety of 3-hydroxykynurenine. Ultra-performance liquid chromatography-tandem mass spectrometry analyses showed that kynoxazine is present in the human lens at levels ranging from 0 to 64 pmol/mg lens. Kynoxazine as well as erythrulose degraded under physiological conditions to generate 3-deoxythreosone, which modified and cross-linked proteins through the formation of an arginine adduct, 3-deoxythreosone-derived hydroimidazolone, and a lysine-arginine cross-linking adduct, 3-deoxythreosone-derived hydroimidazolimine cross-link. Ultra-performance liquid chromatography-tandem mass spectrometry quantification showed that 32-169 pmol/mg protein of 3-deoxythreosone-derived hydroimidazolone and 1.1-11.2 pmol/mg protein of 3-deoxythreosone-derived hydroimidazolimine cross-link occurred in aging lenses. Taken together, these results demonstrate a novel biochemical mechanism by which ascorbate oxidation and the kynurenine pathway intertwine, which could promote protein modification and cross-linking in aging human lenses. PMID:26941078

  10. 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

  11. 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. PMID:25913071

  12. Obesity accelerates epigenetic aging of human liver.

    PubMed

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

    2014-10-28

    Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an "epigenetic clock") to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10(-4) in dataset 1 and r = 0.42, P = 1.2 × 10(-4) in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10(-9)) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer. PMID:25313081

  13. 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.

  14. Human ageing and the sympathoadrenal system.

    PubMed

    Seals, D R; Esler, M D

    2000-11-01

    Over the past three decades the changes in sympathoadrenal function that occur with age in healthy adult humans have been systematically studied using a combination of neurochemical, neurophysiological and haemodynamic experimental approaches. The available experimental evidence indicates that tonic whole-body sympathetic nervous system (SNS) activity increases with age. The elevations in SNS activity appear to be region specific, targeting skeletal muscle and the gut, but not obviously the kidney. The SNS tone of the heart is increased, although this appears to be due in part to reduced neuronal reuptake of noradrenaline (norepinephrine). In contrast to SNS activity, tonic adrenaline (epinephrine) secretion from the adrenal medulla is markedly reduced with age. This is not reflected in plasma adrenaline concentrations because of reduced plasma clearance. Despite widely held beliefs to the contrary, sympathoadrenal responsiveness to acute stress is not exaggerated with age in healthy adults. Indeed, adrenaline release in response to acute stress is substantially attenuated in older men. The mechanisms underlying the age-associated increases in SNS activity have not been established, but our preliminary data are consistent with increased subcortical central nervous system (CNS) sympathetic drive. These changes in sympathoadrenal function with advancing age may have a number of important physiological and pathophysiological consequences for human health and disease. PMID:11060120

  15. Cardiovascular Aging: Perspectives From Humans to Rodents.

    PubMed

    Lakatta, Edward G.

    1998-11-01

    In order to define and target the specific characteristics of cardiovascular aging that render aging as a risk factor for diseases (such as atherosclerosis, hypertension, stroke, and heart failure) that reach epidemic proportions among older individuals, it is essential to develop quantitative information on age-associated alterations in cardiovascular structure and function in health. A sustained effort, over the past two decades, has been applied to characterize the multiple effects of aging on health in cardiovascular structure and function in a single study population (BLSA). In these studies, community-dwelling, volunteer participants are rigorously screened to detect both clinical and occult cardiovascular disease and characterized with respect to lifestyle (e.g., exercise habits), in an attempt to deconvolute interactions among lifestyle, cardiovascular disease, and the aging process in health. Some specific changes in resting cardiovascular structure and function and cardiovascular reserve capacity that occur with advancing age in these healthy humans have been identified and are presented here. These observations in humans are extended by relevant experiments from animal models to provide possible mechanistic insight.

  16. Primate lens capsule elasticity assessed using Atomic Force Microscopy.

    PubMed

    Ziebarth, Noël M; Arrieta, Esdras; Feuer, William J; Moy, Vincent T; Manns, Fabrice; Parel, Jean-Marie

    2011-06-01

    The purpose of this project is to measure the elasticity of the human and non-human primate lens capsule at the microscopic scale using Atomic Force Microscopy (AFM). Elasticity measurements were performed using AFM on the excised anterior lens capsule from 9 cynomolgus monkey (5.9-8.0 years), 8 hamadryas baboon (2.8-10.1 years), and 18 human lenses (33-79 years). Anterior capsule specimens were obtained by performing a 5 mm continuous curvilinear capsulorhexis and collecting the resulting disk of capsular tissue. To remove the lens epithelial cells the specimen was soaked in 0.1% trypsin and 0.02% EDTA for 5 min, washed, and placed on a Petri dish and immersed in DMEM. Elasticity measurements of the capsule were performed with a laboratory-built AFM system custom designed for force measurements of ophthalmic tissues. The capsular specimens were probed with an AFM cantilever tip to produce force-indentation curves for each specimen. Young's modulus was calculated from the force-indentation curves using the model of Sneddon for a conical indenter. Young's modulus of elasticity was 20.1-131 kPa for the human lens capsule, 9.19-117 kPa for the cynomolgus lens capsule, and 13.1-62.4 kPa for the baboon lens capsule. Young's modulus increased significantly with age in humans (p = 0.03). The age range of the monkey and baboon samples was not sufficient to justify an analysis of age dependence. The capsule elasticity of young humans (<45 years) was not statistically different from that of the monkey and baboon. In humans, there is an increase in lens capsule stiffness at the microscale that could be responsible for an increase in lens capsule bulk stiffness.

  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. PMID:18184876

  18. 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

  19. 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

  20. Effects of a novel DNA methyltransferase inhibitor Zebularine on human lens epithelial cells

    PubMed Central

    Zhou, Peng; Sun, Xing-Huai

    2012-01-01

    Purpose Posterior capsular opacification (PCO) is a common long-term complication of modern cataract surgery. We have shown that Zebularine, an inhibitor of DNA methylation, suppresses transforming growth factor-β (TGFβ)-induced lens epithelial cells (LECs)–myofibroblasts transdifferentiation. The purpose of this study is to evaluate the role that Zebularine plays in the inhibition of PCO pathogenesis, including its effect on attachment, migration, and proliferation of LECs in vitro. Methods A tetrazolium dye–reduction assay (MTT test) was performed to determine cell proliferation. Cell attachment was assessed by modified MTT test. Migration was determined by the transwell method after incubation of LECs with Zebularine. The effect of Zebularine on DNA-methyltransferase 1 (DNMT1), phospho-p44/42 Map Kinase, and protein kinase B (Akt) were analyzed by western blot. Results Zebularine was an effective inhibitor of human LEC proliferation, attachment, and migration in vitro. A Zebularine concentration of 100 μM accounted for the following: inhibition of cell proliferation of 57.2%, reduction in cell attachment to 29.6%, and inhibition of cell migration of 58.9%. All effects were dose dependent. Zebularine treatment resulted in dose-dependent decreases of DNMT1, phosphorylated p44/42 MAP Kinase, and phosphorylated Akt. Conclusions Zebularine is capable of inhibiting the crucial cellular events in PCO pathogenesis in vitro. Zebularine acts through the inhibition of DNMT1, and it consequently down regulation of the expression of proliferative and survival genes that relate to pathogenesis of PCO. These findings suggest that Zebularine may become a therapeutic approach for the prevention of PCO. PMID:22259221

  1. 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.

  2. 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.

  3. 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. PMID:26764332

  4. Noncoding Transcriptional Landscape in Human Aging.

    PubMed

    Costa, Marina C; Leitão, Ana Lúcia; Enguita, Francisco J

    2016-01-01

    Aging is a universal phenomenon in metazoans, characterized by a general decline of the organism physiology associated with an increased risk of mortality and morbidity. Aging of an organism correlates with a decline in function of its cells, as shown for muscle, immune, and neuronal cells. As the DNA content of most cells within an organism remains largely identical throughout the life span, age-associated transcriptional changes must be achieved by epigenetic mechanisms. However, how aging may impact on the epigenetic state of cells is only beginning to be understood. In light of a growing number of studies demonstrating that noncoding RNAs can provide molecular signals that regulate expression of protein-coding genes and define epigenetic states of cells, we hypothesize that noncoding RNAs could play a direct role in inducing age-associated profiles of gene expression. In this context, the role of long noncoding RNAs (lncRNAs) as regulators of gene expression might be important for the overall transcriptional landscape observed in aged human cells. The possible functions of lncRNAs and other noncoding RNAs, and their roles in the regulation of aging-related cellular pathways will be analyzed.

  5. 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. PMID:22304987

  6. Dose conversion coefficients for electron exposure of the human eye lens

    NASA Astrophysics Data System (ADS)

    Behrens, R.; Dietze, G.; Zankl, M.

    2009-07-01

    Recent epidemiological studies suggest a rather low dose threshold (below 0.5 Gy) for the induction of a cataract of the eye lens. Some other studies even assume that there is no threshold at all. Therefore, protection measures have to be optimized and current dose limits for the eye lens may be reduced in the future. Two questions arise from this situation: first, which dose quantity is related to the risk of developing a cataract, and second, which personal dose equivalent quantity is appropriate for monitoring this dose quantity. While the dose equivalent quantity Hp(0.07) has often been seen as being sufficiently accurate for monitoring the dose to the lens of the eye, this would be questionable in the case when the dose limits were reduced and, thus, it may be necessary to generally use the dose equivalent quantity Hp(3) for this purpose. The basis for a decision, however, must be the knowledge of accurate conversion coefficients from fluence to equivalent dose to the lens. This is especially important for low-penetrating radiation, for example, electrons. Formerly published values of conversion coefficients are based on quite simple models of the eye. In this paper, quite a sophisticated model of the eye including the inner structure of the lens was used for the calculations and precise conversion coefficients for electrons with energies between 0.2 MeV and 12 MeV, and for angles of radiation incidence between 0° and 45° are presented. Compared to the values adopted in 1996 by the International Commission on Radiological Protection (ICRP), the new values are up to 1000 times smaller for electron energies below 1 MeV, nearly equal at 1 MeV and above 4 MeV, and by a factor of 1.5 larger at about 1.5 MeV electron energy.

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

    PubMed

    Chhabra, Mahendra; Prausnitz, John M; Radke, C J

    2009-07-01

    The rate of oxygen consumption is an important parameter to assess the physiology of the human cornea. Metabolism of oxygen in the cornea is influenced by contact-lens-induced hypoxia, diseases such as diabetes, surgery, and drug treatment. Therefore, estimation of in vivo corneal oxygen-consumption rate is essential for gauging adequate oxygen supply to the cornea. Phosphorescence quenching of a dye coated on the posterior of a soft contact lens provides a powerful technique to measure tear-film oxygen tension (Harvitt and Bonanno, Invest Ophthalmol Vis Sci 1996;37:1026-1036; Bonanno et al., Invest Ophthalmol Vis Sci 2002;43:371-376). Unfortunately, previous work in establishing oxygen-consumption kinetics from transient postlens tear-film oxygen tensions relies on the simplistic assumption of a constant corneal-consumption rate. A more realistic model of corneal metabolism is needed to obtain reliable oxygen-consumption kinetics. Here, physiologically relevant nonlinear Monod kinetics is adopted for describing the local oxygen-consumption rate, thus avoiding aphysical negative oxygen tensions in the cornea. We incorporate Monod kinetics in an unsteady-state reactive-diffusion model for the cornea contact-lens system to determine tear-film oxygen tension as a function of time when changing from closed-eye to open-eye condition. The model was fit to available experimental data of in vivo human postlens tear-film oxygen tension to determine the corneal oxygen-consumption rate. Reliance on corneal oxygen diffusivity and solubility data obtained from rabbits is no longer requisite. Excellent agreement is obtained between the proposed model and experiment. We calculate the spatial-averaged in vivo human maximum corneal oxygen-consumption rate as Q(c)(max) = 1.05 x 10(-4) mL/(cm(3) s). The calculated Monod constant is K(m) = 2.2 mmHg.

  8. 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.

  9. Failure to withstand oxidative stress induced by phospholipid hydroperoxides as a possible cause of the lens opacities in systemic diseases and ageing.

    PubMed

    Babizhayev, M A

    1996-03-01

    Lipid peroxidation (LPO) is a causative factor of cataract. The increased concentrations of primary molecular LPO products (diene conjugates, lipid hydroperoxides) and end fluorescent LPO products, were detected in the lipid moieties of the aqueous humor samples obtained from patients with senile and complicated cataracts as compared to normal donors. The degrees of lens clouding were assessed quantitatively by measuring the optical density indices and areas of equidensities using digital image analysis. Human cataractous lenses showed decreased activity of glutathione peroxidase (GPX, catalyzing reduction of organic hydroperoxides including hydroperoxides of lipids). The apparent Km for tert-butylhydroperoxide was 0.434 mM for human normal and cataractous lens GPX. When lenses were exposed for 1 h at 37 degrees C to linoleic acid hydroperoxide (LOOH, 0.5 mM) or egg phosphatidyl-choline hydroperoxide (PLOOH, 1 micro mol per 112 micro mol of phospholipid) in liposomes suspended in the incubation medium, normal, immature and mature human cataractous lenses showed a significant loss in the residual content of liberated LOOH to 62%, 38% or 17%, correspondingly, but little or no reduction was observed with PLOOH in liposomal membranes. Human, rabbit or mice transparent or immature cataractous lenses induced significantly more absorbance changes in conjugated diene, iodometric and TBA-reactive substance measurements when incubated with liposomal membranes which were decreased in the presence of free radical scavengers and antioxidant enzymes (EDTA, SOD, L-carnosine, chelated iron, catalase). Injection into the vitreous body of the rabbit eye of a suspension of liposomes prepared from phospholipids containing LPO products induced the development of posterior subcapsular cataract. Saturated liposomes did not cause clouding of the lens. This modelling of cataract was accompanied by accumulation of fluorescing LPO products in the vitreous body, aqueous humor and the lens and

  10. 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.

  11. 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

  12. Chronological ageing of human hair keratin fibres.

    PubMed

    Thibaut, S; de Becker, E; Bernard, B A; Huart, M; Fiat, F; Baghdadli, N; Luengo, G S; Leroy, F; Angevin, P; Kermoal, A M; Muller, S; Peron, M; Provot, G; Kravtchenko, S; Saint-Léger, D; Desbois, G; Gauchet, L; Nowbuth, K; Galliano, A; Kempf, J Y; Silberzan, I

    2010-12-01

    Examination of very long hair (length > 2.4 m) using a large range of evaluation methods including physical, chemical, biochemical and microscopic techniques has enabled to attain a detailed understanding of natural ageing of human hair keratin fibres. Scrutinizing hair that has undergone little or no oxidative aggression--because of the absence of action of chemical agents such as bleaching or dyeing--from the root to the tip shows the deterioration process, which gradually takes place from the outside to the inside of the hair shaft: first, a progressive abrasion of the cuticle, whilst the cortex structure remains unaltered, is evidenced along a length of roughly 1 m onwards together with constant shine, hydrophobicity and friction characteristics. Further along the fibre, a significant damage to cuticle scales occurs, which correlates well with ceramides and 18-Methyl Eicosanoic Acid (18-MEA) decline, and progressive decrease in keratin-associated protein content. Most physical descriptors of mechanical and optical properties decay significantly. This detailed description of natural ageing of human hair fibres by a fine analysis of hair components and physical parameters in relationship with cosmetic characteristics provides a time-dependent 'damage scale' of human hair, which may help in designing new targeted hair care formulations.

  13. 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.

  14. 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.

  15. Preserving humanity in an age of technology.

    PubMed

    Mann, R E

    1992-03-01

    Preserving humanity in the present technological age can be a challenge for all health care workers, but perhaps particularly for staff working within an intensive care environment. This article highlights some of the potential effects of such technology on staff, patients and relatives, particularly bringing to light some of the disadvantages brought about by the use of such technology. Areas considered include the role of nurses within a technological environment, patients' and relatives' reactions to technology, the potential effect on autonomy and responsibility for both patients and nurses, economic issues, and finally ethical and moral issues raised by the advent of further technology. Despite many positive contributions to nursing care which arise from the use of technology, there are disadvantages attributed to technology which have only been mentioned superficially in previous literature on this subject. The question arises as to whether nurses are able to balance preserving the humanity of patients with the extensive use of technology in an intensive care environment today.

  16. GENETICS OF HUMAN AGE RELATED DISORDERS.

    PubMed

    Srivastava, I; Thukral, N; Hasija, Y

    2015-01-01

    Aging is an inevitable biological phenomenon. The incidence of age related disorders (ARDs) such as cardiovascular diseases, cancer, arthritis, dementia, osteoporosis, diabetes, neurodegenerative diseases increase rapidly with aging. ARDs are becoming a key social and economic trouble for the world's elderly population (above 60 years), which is expected to reach 2 billion by 2050. Advancement in understanding of genetic associations, particularly through genome wide association studies (GWAS), has revealed a substantial contribution of genes to human aging and ARDs. In this review, we have focused on the recent understanding of the extent to which genetic predisposition may influence the aging process. Further analysis of the genetic association studies through pathway analysis several genes associated with multiple ARDs have been highlighted such as apolipoprotein E (APOE), brain-derived neurotrophic factor (BDNF), cadherin 13 (CDH13), CDK5 regulatory subunit associated protein 1 (CDKAL-1), methylenetetrahydrofolate reductase (MTHFR), disrupted in schizophrenia 1 (DISC1), nitric oxide synthase 3 (NOS3), paraoxonase 1 (PON1), indicating that these genes could play a pivotal role in ARD causation. These genes were found to be significantly enriched in Jak-STAT signalling pathway, asthma and allograft rejection. Further, interleukin-6 (IL-6), insulin (INS), vascular endothelial growth factor A (VEGFA), estrogen receptor1 (ESR1), transforming growth factor, beta 1(TGFB1) and calmodulin 1 (CALM1) were found to be highly interconnected in network analysis. We believe that extensive research on the presence of common genetic variants among various ARDs may facilitate scientists to understand the biology behind ARDs causation. PMID:26856084

  17. 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.

  18. 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

  19. EPHA2 Is Associated with Age-Related Cortical Cataract in Mice and Humans

    PubMed Central

    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

    2009-01-01

    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. PMID:19649315

  20. Refractive Power and Biometric Properties of the Nonhuman Primate Isolated Crystalline Lens

    PubMed Central

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

    2010-01-01

    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. PMID:20107174

  1. Collagens in the aged human macula.

    PubMed

    Marshall, G E; Konstas, A G; Reid, G G; Edwards, J G; Lee, W R

    1994-03-01

    Immunogold cytochemistry was used to investigate the fine structural distribution of collagen types I-VI in Bruch's membrane and choroid of the aged human macula. Macular tissue was obtained from ten eyes, and processed for cryoultramicrotomy and London Resin white embedding. Striated collagen fibrils within the inner and outer collagenous layers were found to contain collagen types I, III and V. In addition, type V collagen was also present in the basement membrane of the choriocapillaris. Gross thickening of the choriocapillaris basement membrane was attributed to the deposition of type IV collagen. However, type IV collagen appeared to be absent from the basement membrane of the retinal pigment epithelium. The interesting location of type VI collagen on the choroidal side of the choriocapillaris suggested that its function is to anchor the choriocapillaris onto the choroid. The collagens studied were absent from fibrous banded material, long-spacing collagen, the elastic layer and amorphous granular material. It was concluded that, of the collagen types studied, only the deposition of type IV collagen contributes to the age-related thickening of Bruch's membrane.

  2. Modulating Human Aging and Age-Associated Diseases

    PubMed Central

    Fontana, Luigi

    2009-01-01

    Population aging is progressing rapidly in many industrialized countries. The United States population aged 65 and over is expected to double in size within the next 25 years. In sedentary people eating Western diets aging is associated with the development of serious chronic diseases, including type 2 diabetes mellitus, cancer and cardiovascular diseases. About 80 percent of adults over 65 years of age have at least one chronic disease, and 50 percent have at least two chronic diseases. These chronic diseases are the most important cause of illness and mortality burden, and they have become the leading driver of healthcare costs, constituting an important burden for our society. Data from epidemiological studies and clinical trials indicate that many age-associated chronic diseases can be prevented, and even reversed, with the implementation of healthy lifestyle interventions. Several recent studies suggest that more drastic interventions (i.e. calorie restriction without malnutrition and moderate protein restriction with adequate nutrition) may have additional beneficial effects on several metabolic and hormonal factors that are implicated in the biology of aging itself. Additional studies are needed to understand the complex interactions of factors that regulate aging and age-associated chronic disease. PMID:19364477

  3. 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. PMID:25713787

  4. 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.

  5. UVA Light-excited Kynurenines Oxidize Ascorbate and Modify Lens Proteins through the Formation of Advanced Glycation End Products

    PubMed Central

    Linetsky, Mikhail; Raghavan, Cibin T.; Johar, Kaid; Fan, Xingjun; Monnier, Vincent M.; Vasavada, Abhay R.; Nagaraj, Ram H.

    2014-01-01

    Advanced glycation end products (AGEs) contribute to lens protein pigmentation and cross-linking during aging and cataract formation. In vitro experiments have shown that ascorbate (ASC) oxidation products can form AGEs in proteins. However, the mechanisms of ASC oxidation and AGE formation in the human lens are poorly understood. Kynurenines are tryptophan oxidation products produced from the indoleamine 2,3-dioxygenase (IDO)-mediated kynurenine pathway and are present in the human lens. This study investigated the ability of UVA light-excited kynurenines to photooxidize ASC and to form AGEs in lens proteins. UVA light-excited kynurenines in both free and protein-bound forms rapidly oxidized ASC, and such oxidation occurred even in the absence of oxygen. High levels of GSH inhibited but did not completely block ASC oxidation. Upon UVA irradiation, pigmented proteins from human cataractous lenses also oxidized ASC. When exposed to UVA light (320–400 nm, 100 milliwatts/cm2, 45 min to 2 h), young human lenses (20–36 years), which contain high levels of free kynurenines, lost a significant portion of their ASC content and accumulated AGEs. A similar formation of AGEs was observed in UVA-irradiated lenses from human IDO/human sodium-dependent vitamin C transporter-2 mice, which contain high levels of kynurenines and ASC. Our data suggest that kynurenine-mediated ASC oxidation followed by AGE formation may be an important mechanism for lens aging and the development of senile cataracts in humans. PMID:24798334

  6. Anomalous radiocarbon ages from a Holocene detrital organic lens in Alaska and their implications for radiocarbon dating and paleoenvironmental reconstructions in the arctic

    USGS Publications Warehouse

    Nelson, R.E.; Carter, L.D.; Robinson, S.W.

    1988-01-01

    Eleven radiocarbon age determinations clearly show that a lens of Holocene fluvial organic debris on the Alaskan Arctic Coastal Plain contains mostly pre-Holocene organic material. Radio-carbon ages of identified plant macrofossils indicate the material was deposited about 9000 to 9500 yr B.P. Radiocarbon analyses of bulk samples from this deposit, however, range from 13,300 to 30,300 yr B.P. Most of the old organic matter seems to be in the smaller size fractions in the deposit, particularly in the fraction between 0.25 and 0.5 mm, but all size fractions are contaminated. Particular caution must be exercised in submitting bulk samples for radiocarbon dating from areas where conditions favor redeposition of isotopically "dead" carbon. ?? 1988.

  7. Mitochondrial "movement" and lens optics following oxidative stress from UV-B irradiation: cultured bovine lenses and human retinal pigment epithelial cells (ARPE-19) as examples.

    PubMed

    Bantseev, Vladimir; Youn, Hyun-Yi

    2006-12-01

    Mitochondria provide energy generated by oxidative phosphorylation and at the same time play a central role in apoptosis and aging. As a byproduct of respiration, the electron transport chain is known to be the major intracellular site for the generation of reactive oxygen species (ROS). Exposure to solar and occupational ultraviolet (UV) radiation, and thus production of ROS and subsequent cell death, has been implicated in a large spectrum of skin and ocular pathologies, including cataract. Retinal pigment epithelial cell apoptosis generates photoreceptor dysfunction and ultimately visual impairment. The purpose of this article was to characterize in vitro changes following oxidative stress with UV-B radiation in (a) ocular lens optics and cellular function in terms of mitochondrial dynamics of bovine lens epithelium and superficial cortical fiber cells and (b) human retinal pigment epithelial (ARPE-19) cells. Cultured bovine lenses and confluent cultures of ARPE-19 cells were irradiated with broadband UV-B radiation at energy levels of 0.5 and 1.0 J/cm(2). Lens optical function (spherical aberration) was monitored daily up to 14 days using an automated laser scanning system that was developed at the University of Waterloo. This system consists of a single collimated scanning helium-neon laser source that projects a thin (0.05 mm) laser beam onto a plain mirror mounted at 45 degrees on a carriage assembly. This mirror reflects the laser beam directly up through the scanner table surface and through the lens under examination. A digital camera captures the actual position and slope of the laser beam at each step. When all steps have been made, the captured data for each step position is used to calculate the back vertex distance for each position and the difference in that measurement between beams. To investigate mitochondrial movement, the mitochondria-specific fluorescent dye Rhodamine 123 was used. Time series were acquired with a Zeiss 510 (configuration Meta

  8. 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.

  9. 21 CFR 886.3600 - Intraocular lens.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Intraocular lens. 886.3600 Section 886.3600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Prosthetic Devices § 886.3600 Intraocular lens. (a) Identification. An intraocular lens is a device made of materials...

  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

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

    2016-04-12

    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. 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

  14. Efficient Generation of Lens Progenitor Cells from Cataract Patient–Specific Induced Pluripotent Stem Cells

    PubMed Central

    Qiu, Xiaodi; Yang, Jin; Liu, Tianjin; Jiang, Yongxiang; Le, Qihua; Lu, Yi

    2012-01-01

    The development of a technique to induce the transformation of somatic cells to a pluripotent state via the ectopic expression of defined transcription factors was a transformational event in the field of regenerative medicine. The development of this technique also impacted ophthalmology, as patient-specific induced pluripotent stemcells (iPSCs) may be useful resources for some ophthalmological diseases. The lens is a key refractive element in the eye that focuses images of the visual world onto the retina. To establish a new model for drug screening to treat lens diseases and investigating lens aging and development, we examined whether human lens epithelial cells (HLECs) could be induced into iPSCs and if lens-specific differentiation of these cells could be achieved under defined chemical conditions. We first efficiently reprogrammed HLECs from age-related cataract patients to iPSCs with OCT-4, SOX-2, and KLF-4. The resulting HLEC-derived iPS (HLE-iPS) colonies were indistinguishable from human ES cells with respect to morphology, gene expression, pluripotent marker expression and their ability to generate all embryonic germ-cell layers. Next, we performed a 3-step induction procedure: HLE-iPS cells were differentiated into large numbers of lens progenitor-like cells with defined factors (Noggin, BMP and FGF2), and we determined that these cells expressed lens-specific markers (PAX6, SOX2, SIX3, CRYAB, CRYAA, BFSP1, and MIP). In addition, HLE-iPS-derived lens cells exhibited reduced expression of epithelial mesenchymal transition (EMT) markers compared with human embryonic stem cells (hESCs) and fibroblast-derived iPSCs. Our study describes a highly efficient procedure for generating lens progenitor cells from cataract patient HLEC-derived iPSCs. These patient-derived pluripotent cells provide a valuable model for studying the developmental and molecular biological mechanisms that underlie cell determination in lens development and cataract pathophysiology

  15. GenAge: a genomic and proteomic network map of human ageing.

    PubMed

    de Magalhães, João Pedro; Toussaint, Olivier

    2004-07-30

    The aim of this work was to provide an overview of the genetics of human ageing to gain novel insights about the mechanisms involved. By incorporating findings from model organisms to humans, such as mutations that either delay or accelerate ageing in mice, we constructed the gene networks previously related to ageing: namely, the network related to DNA metabolism and the network involving the GH/IGF-1 axis. Gathering data about the interacting partners of these proteins allowed us to suggest the involvement in ageing of a number of proteins through a "guilt-by-association" methodology. To organize our data, we developed the first curated database of genes related to human ageing: GenAge. With over 200 entries, GenAge may serve as a reference database of genes related to human ageing. Moreover, we rendered the first proteomic network map of human ageing, which suggests a relationship between the genetics of development and the genetics of ageing. Our work serves as a framework upon which a systems-biology understanding of ageing can be developed. GenAge is freely available for academic purposes at: http://genomics.senescence.info/genes/.

  16. 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

  17. 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…

  18. Age, human performance, and physical employment standards.

    PubMed

    Kenny, Glen P; Groeller, Herbert; McGinn, Ryan; Flouris, Andreas D

    2016-06-01

    The proportion of older workers has increased substantially in recent years, with over 25% of the Canadian labour force aged ≥55 years. Along with chronological age comes age-related declines in functional capacity associated with impairments to the cardiorespiratory and muscular systems. As a result, older workers are reported to exhibit reductions in work output and in the ability to perform and/or sustain the required effort when performing work tasks. However, research has presented some conflicting views on the consequences of aging in the workforce, as physically demanding occupations can be associated with improved or maintained physical function. Furthermore, the current methods for evaluating physical function in older workers often lack specificity and relevance to the actual work tasks, leading to an underestimation of physical capacity in the older worker. Nevertheless, industry often lacks the appropriate information and/or tools to accommodate the aging workforce, particularly in the context of physical employment standards. Ultimately, if appropriate workplace strategies and work performance standards are adopted to optimize the strengths and protect against the vulnerability of the aging workers, they can perform as effectively as their younger counterparts. Our aim in this review is to evaluate the impact of different individual (including physiological decline, chronic disease, lifestyle, and physical activity) and occupational (including shift work, sleep deprivation, and cold/heat exposure) factors on the physical decline of older workers, and therefore the risk of work-related injuries or illness. PMID:27277571

  19. Human neurologic function and the aging process.

    PubMed

    Potvin, A R; Syndulko, K; Tourtellotte, W W; Lemmon, J A; Potvin, J H

    1980-01-01

    Sixty-one normal men whose ages ranged from 20 to 80 years were evaluated on two occasions by means of a comprehensive series of 128 instrumented tests of neurologic function. The tests measured cognition, vision, strength, steadiness, reactions, speed, coordination, fatigue, gait, station, sensations, and tasks of daily living. The reliability of each test measured was determined, and any measure found unreliable (r less than or equal to 0.41) was not further analyzed. Significant age-related linear decreases were found for almost all neurologic functions. The declines over the age span varied from less than 10 percent to more than 90 percent for different functions. For the upper extremities, the largest declines (greater than 50 percent) were in hand-force steadiness, speed of hand-arm movements, and vibration sense; for the lower extremities, the largest declines were in one-legged balance with eyes closed and in vibration sense. For 13 of 14 tests in which significant dominant body-side effects were found, larger re-testing 7-10 days later, the subjects improved their scores by more than 5 percent on only 17 tests, 9 of which concerned the activities of daily living. No significant differential learning effects were found across age groups. The results point to the importance of developing a data bank on age-based neurologic function so that therapeutic effects can be evaluated in terms of age- and sex-matched normal functioning.

  20. Examination of the effect of the fibrous structure of a lens on the optical characteristics of the human eye: a computer-simulated model

    NASA Astrophysics Data System (ADS)

    Al-Ahdali, Issam H.; El-Messiery, M. A.

    1995-09-01

    We introduce a model of the human eye for which we take into consideration the laminated nature of lens fibers. The thickness of each lamina is 5.6 mu m; thus the lens comprises 300 eccentric lenses of minute dimensions. The index gradient of the lens is such that the index of refraction increases exponentially from the lens core to its peripheral zone. A vector ray-tracing technique is employed to study the optical characteristics of the system. Both paraxial and marginal rays are simulated, and the angles of incidence vary from 0 deg to +/-20 deg. Special attention is given to the meridional caustic surfaces as well as the wave-front distortion of the refracted rays. A quasi-Newton optimization technique is employed to obtain the best parameters for the system. A computer modeling program, written in fortran 77, is used to simulate a ray's refraction through the multisurfaces of the eye. The results show full agreement with previous data and that the cornea is responsible for eliminating possible spherical aberration of the system.

  1. 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

  2. TGF-β2 induces transdifferentiation and fibrosis in human lens epithelial cells via regulating gremlin and CTGF.

    PubMed

    Ma, Bo; Kang, Qianyan; Qin, Li; Cui, Lijun; Pei, Cheng

    2014-05-16

    Transforming growth factor (TGF)-β2, gremlin and connective tissue growth factor (CTGF) are known to play important roles in the induction of epithelial mesenchymal transition (EMT) and extracellular matrix (ECM) synthesis. However, the complex functional relationship among gremlin, CTGF and TGF-β2 in the induction of EMT and ECM synthesis in human lens epithelial cells (HLECs) has not been reported. In this study, we found that TGF-β2, CTGF and gremlin can individually induce the expression of α-smooth muscle actin (α-SMA), fibronectin (Fn), collagen type I (COL-I), Smad2 and Smad3 in HLECs. Blockade of CTGF and gremlin effectively inhibited TGF-β2-induced expression of α-SMA, Fn, COL-I, Smad2, and Smad3 in HLECs. Furthermore blockade of Smad2 and Smad3 effectively inhibited CTGF and gremlin induced expression of α-SMA, Fn, COL-I in HLECs. In conclusion, TGF-β2, CTGF and gremlin are all involved in EMT and ECM synthesis via activation of Smad signaling pathway in HLECs. Specifically silencing CTGF and gremlin can effectively block the TGF-β2-induced EMT, ECM synthesis due to failure in activation of Smad signaling pathway in HLECs.

  3. Oxidative stress in aging human skin.

    PubMed

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

    2015-04-21

    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.

  4. 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

  5. [Biofunctional age diagnosis in humans. Potentials and limits].

    PubMed

    Pöthig, D; Gerdes, W; Viol, M; Wagner, P; Simm, A

    2011-06-01

    The demand and requirements for valid, practicable, and reliable procedures for age diagnosis are increasing worldwide. In contrast, few studies and only a small number of procedures exist. The authors review the theoretical and methodological requirements for the development of models for age diagnostics. They describe the fundamentals for further studies, based on an analysis of current gerontological research in this area. A following publication will report the valid systems measuring vitality and biofunctional age(ing) of human beings. PMID:21505938

  6. DNA-related pathways defective in human premature aging.

    PubMed

    Bohr, Vilhelm A

    2002-05-07

    One of the major issues in studies on aging is the choice of biological model system. The human premature aging disorders represent excellent model systems for the study of the normal aging process, which occurs at a much earlier stage in life in these individuals than in normals. The patients with premature aging also get the age associated diseases at an early stage in life, and thus age associated disease can be studied as well. It is thus of great interest to understand the molecular pathology of these disorders.

  7. THE ANOREXIA OF AGING IN HUMANS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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), psycholog...

  8. 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

  9. Variable domain structure of {kappa}IV human light chain len : high homology to the murine light chain McPC603.

    SciTech Connect

    Huang, D.-B.; Chang, C.-H.; Ainsworth, C.; Johnson, G.; Solomon, A.; Stevens, F. J.; Schiffer, M.; Center for Mechanistic Biology and Biotechnology; Univ. of Tennessee Medical Center

    1997-12-01

    Antibody light chains of the {kappa} subgroup are the predominant light chain component in human immune responses and are used almost exclusively in the antibody repertoire of mice. Human {kappa} light chains comprise four subgroups. To date, all crystallographic studies of human {kappa} light chains were carried out on proteins of the {kappa}I subgroup. The light chain produced by multiple myeloma patient Len, was of the {kappa}IV subgroup, it differed by only one residue from the germ-line gene encoded protein. The variable domain fragment of the light chain was crystallized from ammonium sulfate in space group C222{sub 1}. The crystal structure was determined by molecular replacement and refined at 1.95 Angstrom resolution to an R-factor of 0.15. Protein Len has six additional residues in its CDR1 segment compared to the {kappa}I proteins previously characterized. The {kappa}IV variable domain. Len, differs in only 23 of 113 residues from murine {kappa} light chain McPC603. The RMS deviation upon superimposing their {alpha}-carbons was 0.69 Angstrom. The CDR1 segment of the human and murine variable domains have the same length and conformation although their amino acid sequences differ in 5 out of 17 residues. Structural features were identified that could account for the significantly higher stability of the human {kappa}IV protein relative to its murine counterpart. This human {kappa}IV light chain structure is the closest human homolog to a murine light chain and can be expected to facilitate detailed structural comparisons necessary for effective humanization of murine antibodies.

  10. Aging of the Human Vestibular System.

    PubMed

    Zalewski, Christopher K

    2015-08-01

    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

  11. Aging of the Human Vestibular System

    PubMed Central

    Zalewski, Christopher K.

    2015-01-01

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

  12. A golden age of human pigmentation genetics.

    PubMed

    Sturm, Richard A

    2006-09-01

    The zebrafish golden mutation is characterized by the production of small and irregular-shaped melanin granules, resulting in a lightening of the pigmented lateral stripes of the animal. The recent positional cloning and localization of the golden gene, combined with genotype-phenotype correlations of alleles of its human orthologue (SLC24A5) in African-American and African-Caribbean populations, provide insights into the genetic and molecular basis of human skin colour. SLC24A5 promotes melanin deposition through maturation of the melanosome, highlighting the importance of ion-exchange in the function of this organelle.

  13. 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

  14. Biochemical markers of aging for longitudinal studies in humans.

    PubMed

    Engelfriet, Peter M; Jansen, Eugène H J M; Picavet, H Susan J; Dollé, Martijn E T

    2013-01-01

    Much progress has been made in the past decades in unraveling the mechanisms that are responsible for aging. The discovery that particular gene mutations in experimental species such as yeast, flies, and nematodes are associated with longevity has led to many important insights into pathways that regulate aging processes. However, extrapolating laboratory findings in experimental species to knowledge that is valid for the complexity of human physiology remains a major challenge. Apart from the restricted experimental possibilities, studying aging in humans is further complicated by the development of various age-related diseases. The availability of a set of biomarkers that really reflect underlying aging processes would be of much value in disentangling age-associated pathology from specific aging mechanisms. In this review, we survey the literature to identify promising biochemical markers of aging, with a particular focus on using them in longitudinal studies of aging in humans that entail repeated measurements on easily obtainable material, such as blood samples. Our search strategy was a 2-pronged approach, one focused on general mechanisms of aging and one including studies on clinical biomarkers of age-related diseases.

  15. Biochemical Markers of Aging for Longitudinal Studies in Humans

    PubMed Central

    Engelfriet, Peter M.; Jansen, Eugène H. J. M.; Picavet, H. Susan J.; Dollé, Martijn E. T.

    2013-01-01

    Much progress has been made in the past decades in unraveling the mechanisms that are responsible for aging. The discovery that particular gene mutations in experimental species such as yeast, flies, and nematodes are associated with longevity has led to many important insights into pathways that regulate aging processes. However, extrapolating laboratory findings in experimental species to knowledge that is valid for the complexity of human physiology remains a major challenge. Apart from the restricted experimental possibilities, studying aging in humans is further complicated by the development of various age-related diseases. The availability of a set of biomarkers that really reflect underlying aging processes would be of much value in disentangling age-associated pathology from specific aging mechanisms. In this review, we survey the literature to identify promising biochemical markers of aging, with a particular focus on using them in longitudinal studies of aging in humans that entail repeated measurements on easily obtainable material, such as blood samples. Our search strategy was a 2-pronged approach, one focused on general mechanisms of aging and one including studies on clinical biomarkers of age-related diseases. PMID:23382477

  16. 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)

  17. 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

    2013-12-01

    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 of

  18. 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

    2013-12-01

    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 of

  19. 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

  20. 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.

  1. HEAT WAVES, AGING, AND HUMAN CARDIOVASCULAR HEALTH

    PubMed Central

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

    2014-01-01

    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 is 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, as well as 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 due to 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 increases the extent of future untoward health outcomes. PMID:24598696

  2. Age-related differences in human skin proteoglycans

    PubMed Central

    Carrino, David A; Calabro, Anthony; Darr, Aniq B; Dours-Zimmermann, Maria T; Sandy, John D; Zimmermann, Dieter R; Sorrell, J Michael; Hascall, Vincent C; Caplan, Arnold I

    2011-01-01

    Previous work has shown that versican, decorin and a catabolic fragment of decorin, termed decorunt, are the most abundant proteoglycans in human skin. Further analysis of versican indicates that four major core protein species are present in human skin at all ages examined from fetal to adult. Two of these are identified as the V0 and V1 isoforms, with the latter predominating. The other two species are catabolic fragments of V0 and V1, which have the amino acid sequence DPEAAE as their carboxyl terminus. Although the core proteins of human skin versican show no major age-related differences, the glycosaminoglycans (GAGs) of adult skin versican are smaller in size and show differences in their sulfation pattern relative to those in fetal skin versican. In contrast to human skin versican, human skin decorin shows minimal age-related differences in its sulfation pattern, although, like versican, the GAGs of adult skin decorin are smaller than those of fetal skin decorin. Analysis of the catabolic fragments of decorin from adult skin reveals the presence of other fragments in addition to decorunt, although the core proteins of these additional decorin catabolic fragments have not been identified. Thus, versican and decorin of human skin show age-related differences, versican primarily in the size and the sulfation pattern of its GAGs and decorin in the size of its GAGs. The catabolic fragments of versican are detected at all ages examined, but appear to be in lower abundance in adult skin compared with fetal skin. In contrast, the catabolic fragments of decorin are present in adult skin, but are virtually absent from fetal skin. Taken together, these data suggest that there are age-related differences in the catabolism of proteoglycans in human skin. These age-related differences in proteoglycan patterns and catabolism may play a role in the age-related changes in the physical properties and injury response of human skin. PMID:20947661

  3. Influence of posterior vitreous detachment and type of intraocular lens on lipid peroxidation in the human vitreous

    PubMed Central

    Nuzzi, Raffaele; Gulino, Giulia Rossana; Versino, Elisabetta; Ghigo, Dario

    2015-01-01

    Purpose The aim of this study was to evaluate the relationship between oxidative stress and human vitreous degeneration, using the presence of an evident posterior vitreous detachment (PVD) as a clinical sign and thiobarbituric acid-reactive substances (TBARS) and nitrite as oxidative biomarkers. Methods We collected 42 vitreous samples from patients undergoing pars plana vitrectomy for two groups of vitreoretinal diseases (macular holes and epimacular membranes). TBARS and nitrite were assessed spectrophotometrically and compared to the presence of an evident PVD, considering other clinical features potentially related to the oxidative stress in the vitreous: diabetes, plasma fibrinogen, type of intraocular lens (IOL), and the vitreoretinal disease requiring the surgery. Results Vitreous TBARS levels were significantly higher in patients with artificial IOLs compared to those with natural lenses and cataracts (1.39±0.64 versus 0.75±0.45; p=0.003). Furthermore, patients with PVD had a significant increase in vitreous TBARS compared to those without PVD (1.45±0.54 versus 0.53±0.38; p=0.001). The plasma fibrinogen levels explained 17% of the TBARS variance, with a significant correlation between these two markers (p=0.011). No significant differences were observed when nitrites were used as biomarkers. Conclusions Current IOLs, even with ultraviolet (UV) absorber, do not ensure the same photoprotection offered by natural lenses affected by corticonuclear cataracts. Furthermore, we observed a relevant correlation between the increased presence of peroxidation products in the vitreous and an evident PVD, but the nature of this relationship requires further study. PMID:26396488

  4. Chronologic versus Biologic Aging of the Human Choroid

    PubMed Central

    May, Christian Albrecht

    2013-01-01

    Several aspects of chronologic and biologic aging in the human choroid are reviewed from the literature. They often reveal methodological problems for age-dependent changes of the following parameters: choroidal thickness, choroidal pigmentation, choroidal vasculature and blood flow, and choroidal innervation. On reinterpreting some data of studies concerning Bruch's membrane, changes observed at different age points seem more likely to be nonlinear. Concluding from the data presented so far, chronologic aging should not be used as a factor for physiological changes in the human choroid. Longitudinal study designs are necessary to further establish the impact of age. Meanwhile, a more biologic oriented model of aging processes in the choroid should be established, including specified conditions (e.g., light exposure and refractory state). This would help to define more individual strategies for prevention and early stages of a certain defined disease. PMID:24453840

  5. Dose conversion coefficients for monoenergetic electrons incident on a realistic human eye model with different lens cell populations

    NASA Astrophysics Data System (ADS)

    Nogueira, P.; Zankl, M.; Schlattl, H.; Vaz, P.

    2011-11-01

    The radiation-induced posterior subcapsular cataract has long been generally accepted to be a deterministic effect that does not occur at doses below a threshold of at least 2 Gy. Recent epidemiological studies indicate that the threshold for cataract induction may be much lower or that there may be no threshold at all. A thorough study of this subject requires more accurate dose estimates for the eye lens than those available in ICRP Publication 74. Eye lens absorbed dose per unit fluence conversion coefficients for electron irradiation were calculated using a geometrical model of the eye that takes into account different cell populations of the lens epithelium, together with the MCNPX Monte Carlo radiation transport code package. For the cell population most sensitive to ionizing radiation—the germinative cells—absorbed dose per unit fluence conversion coefficients were determined that are up to a factor of 4.8 higher than the mean eye lens absorbed dose conversion coefficients for electron energies below 2 MeV. Comparison of the results with previously published values for a slightly different eye model showed generally good agreement for all electron energies. Finally, the influence of individual anatomical variability was quantified by positioning the lens at various depths below the cornea. A depth difference of 2 mm between the shallowest and the deepest location of the germinative zone can lead to a difference between the resulting absorbed doses of up to nearly a factor of 5000 for electron energy of 0.7 MeV.

  6. Mechanism of lens capsular rupture following blunt trauma: a finite element study.

    PubMed

    Liu, Xiaoyu; Wang, Lizhen; Du, Chengfei; Li, Deyu; Fan, Yubo

    2015-01-01

    Blunt impact on the eye could results in lens capsular rupture that allows foreign substances to enter into the lens and leads to cataract formation. This paper aimed to investigate the mechanism of lens capsular rupture using finite element (FE) method. A FE model of the human eye was developed to simulate dynamic response of the lens capsule to a BB (a standard 4.5-mm-diameter pellet) impact. Sensitivity studies were conducted to evaluate the effect of the parameters on capsular rupture, including the impact velocity, the elastic modulus of the lens, the thickness and the elastic modulus of the lens capsule. The results indicated that the lens was subjected to anterior compression and posterior intension when the eye was stricken by a BB pellet. The strain on the posterior capsule (0.392) was almost twice as much as that on the anterior capsule (0.207) at an impact velocity of 20 m/s. The strain on the capsule was proportional to the impact velocity, while the capsular strain showed no significant change when the lens modulus elastic varied with age. The findings confirmed that blunt traumatic capsular rupture is the result of shockwave propagation throughout the eye. The posterior capsule is subjected to greater tension in blunt trauma, which is the main cause that ruptures are more commonly found on the posterior capsule than the anterior capsule. Also, thinner thickness and lower elastic modulus would contribute to the posterior capsular rupture.

  7. Looking for disease being a model of human aging

    PubMed Central

    Hausmanowa-Petrusewicz, I; Madej-Pilarczyk, A

    2007-01-01

    Summary This paper is a part of an introduction to authors’ study on systemic laminopathies and their role in human aging. Of special interest is progeria – a type of systemic laminopathy associated usually with mutation 1824 C > T and presenting phenotype of preliminary aging. The authors analyse the differences between the progeria and other syndrome of preliminary aging – Werner’s syndrome. PMID:18421896

  8. 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.

  9. Effect of Age on Regulation of Human Osteoclast Differentiation

    PubMed Central

    Chung, Ping-Lin; Zhou, Shuanhu; Eslami, Behnam; Shen, Longxiang; LeBoff, Meryl S.; Glowacki, Julie

    2014-01-01

    Human skeletal aging is characterized as a gradual loss of bone mass due to an excess of bone resorption not balanced by new bone formation. Using human marrow cells, we tested the hypothesis that there is an age-dependent increase in osteoclastogenesis due to intrinsic changes in regulatory factors [macrophage-colony stimulating factor (M-CSF), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin (OPG)] and their receptors [c-fms and RANK]. In bone marrow cells (BMCs), c-fms (r=0.61, p=0.006) and RANK expression (r=0.59, p=0.008) were increased with age (27-82 years, n=19). In vitro generation of osteoclasts was increased with age (r=0.89, p=0.007). In enriched marrow stromal cells (MSCs), constitutive expression of RANKL was increased with age (r=0.41, p=0.049) and expression of OPG was inversely correlated with age (r=-0.43, p=0.039). Accordingly, there was an age-related increase in RANKL/OPG (r=0.56, p=0.005). These data indicate an age-related increase in human osteoclastogenesis that is associated with an intrinsic increase in expression of c-fms and RANK in osteoclast progenitors, and, in the supporting MSCs, an increase in pro-osteoclastogenic RANKL expression and a decrease in anti-osteoclastogenic OPG. These findings support the hypothesis that human marrow cells and their products can contribute to skeletal aging by increasing the generation of bone-resorbing osteoclasts. These findings help to explain underlying molecular mechanisms of progressive bone loss with advancing age in humans. PMID:24700654

  10. 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…

  11. 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

  12. Non-contact optical measurement of lens capsule thickness during simulated accommodation

    NASA Astrophysics Data System (ADS)

    Ziebarth, Noel; Manns, Fabrice; Acosta, Ana-Carolina; Parel, Jean-Marie

    2005-04-01

    Purpose: To non-invasively measure the thickness of the anterior and posterior lens capsule, and to determine if it significantly changes during accommodation. Methods: Anterior and posterior capsule thickness was measured on post-mortem lenses using a non-contact optical system using a focus-detection technique. The optical system uses a 670nm laser beam delivered to a single-mode fiber coupler. The output of the fiber coupler is focused on the tissue surface using an aspheric lens (NA=0.68) mounted on a translation stage with a motorized actuator. Light reflected from the sample surface is collected by the fiber coupler and sent to a photoreceiver connected to a computer-controlled data acquisition system. Optical intensity peaks are detected when the aspheric lens is focused on the capsule boundaries. The capsule thickness is equal to the distance traveled between two peaks multiplied by the capsule refractive index. Anterior and posterior lens capsule thickness measurements were performed on 18 cynomolgus (age average: 6+/-1 years, range: 4-7 years) eyes, 1 rhesus (age: 2 years) eye, and 12 human (age average: 65+/-16, range: 47-92) eyes during simulated accommodation. The mounted sample was placed under the focusing objective of the optical system so that the light was incident on the center pole. Measurements were taken of the anterior lens capsule in the unstretched and the stretched 5mm states. The lens was flipped, and the same procedure was performed for the posterior lens capsule. Results: The precision of the optical system was determined to be +/-0.5um. The resolution is 4um and the sensitivity is 52dB. The human anterior lens capsule thickness was 6.0+/-1.2um unstretched and 4.9+/-0.9um stretched (p=0.008). The human posterior lens capsule was 5.7+/-1.2um unstretched and 5.7+/-1.4um stretched (p=0.974). The monkey anterior lens capsule thickness was 5.9+/-1.9um unstretched and 4.8+/-1.0um stretched (p=0.002). The monkey posterior lens capsule was 5

  13. 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.

  14. 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

  15. 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.

  16. Dose conversion coefficients for monoenergetic electrons incident on a realistic human eye model with different lens cell populations.

    PubMed

    Nogueira, P; Zankl, M; Schlattl, H; Vaz, P

    2011-11-01

    The radiation-induced posterior subcapsular cataract has long been generally accepted to be a deterministic effect that does not occur at doses below a threshold of at least 2 Gy. Recent epidemiological studies indicate that the threshold for cataract induction may be much lower or that there may be no threshold at all. A thorough study of this subject requires more accurate dose estimates for the eye lens than those available in ICRP Publication 74. Eye lens absorbed dose per unit fluence conversion coefficients for electron irradiation were calculated using a geometrical model of the eye that takes into account different cell populations of the lens epithelium, together with the MCNPX Monte Carlo radiation transport code package. For the cell population most sensitive to ionizing radiation-the germinative cells-absorbed dose per unit fluence conversion coefficients were determined that are up to a factor of 4.8 higher than the mean eye lens absorbed dose conversion coefficients for electron energies below 2 MeV. Comparison of the results with previously published values for a slightly different eye model showed generally good agreement for all electron energies. Finally, the influence of individual anatomical variability was quantified by positioning the lens at various depths below the cornea. A depth difference of 2 mm between the shallowest and the deepest location of the germinative zone can lead to a difference between the resulting absorbed doses of up to nearly a factor of 5000 for electron energy of 0.7 MeV. PMID:21983644

  17. Electrical properties of human skin as aging biomarkers.

    PubMed

    Simić-Krstić, Jovana B; Kalauzi, Aleksandar J; Ribar, Srdjan N; Matija, Lidija R; Misevic, Gradimir N

    2014-09-01

    A non-invasive bioimpedance spectroscopy (BIS) and Cole-Cole impedance model parameters (R0, R∞, τ and α) were used to analyze electrical properties of intact and stripped human skin for both gender subjects divided into younger and older age groups. R0, R∞ and τ significantly increased while α significantly decreased with age in stripped skin for both genders (p<0.031). Using pooled data with respect to age, gender and skin stripping, R0, R∞ and τ values were shown to increase with age (p<0.0034), R0, τ and α were different between genders (p<0.024) and R0, R∞ and τ decreased with skin stripping (p<0.000008). All of four Cole-Cole parameters were age dependent with specific differences observed for genders and intact and stripped skin layers. Therefore, Cole-Cole parameters, obtained by non-invasive BIS measurements, are a new type of age dependent biomarkers.

  18. Imaging characteristics of ball lens

    NASA Astrophysics Data System (ADS)

    Li, Qinghui; Shao, Xiaopeng

    2014-05-01

    In most digital imaging applications, high-resolution imaging or videos are usually desired for later processing and analysis. The desire for high-resolution stems from two principal application areas: improvement of pictorial information for human interpretation, and helping representation for automatic machine preception. While the image sensors limit the spatial resolution of the image, the image details are also limited by the optical system, due to diffraction, and aberration1. Monocentric lens are an attractive option for gigapixel camera because the symmetrical design focuses light identically coming from any direction. Marks and Brady proposed a monocentric lens design imaging 40 gigapixels with an f-number of 2.5 and resolving 2 arcsec over a 120 degrees field of view2. Recently, Cossairt, Miau, and Nayer proposed a proof-of-concept gigapixel computational camera consisting of a large ball lens shared by several small planar sensors coupled with a deblurring step3. The design consists of a ball element resulting in a lens that is both inexpensive to produce and easy to align. Because the resolution of spherical lens is fundamentally limited by geometric aberrations, the imaging characteristics of the ball lens is expressed by the geometrical aberrations, in which the general equations for the primary aberration of the ball lens are given. The effect of shifting the stop position on the aberrations of a ball lens is discussed. The variation of the axial chromatic aberration with the Abbe V-number when the refraction index takes different values is analyzed. The variation of the third-order spherical aberration ,the fifth-order spherical aberration and the spherical aberration obtained directly from ray tracing with the f-number is discussed. The other imaging evaluation merits, such as the spot diagram, the modulation transfer function(MTF) and the encircled energy are also described. Most of the analysis of the ball lens is carried out using OSLO optics

  19. 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.

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

    SciTech Connect

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

    2015-03-01

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

  1. Age-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

  2. 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.

  3. Age-related changes in mucins from human whole saliva.

    PubMed

    Denny, P C; Denny, P A; Klauser, D K; Hong, S H; Navazesh, M; Tabak, L A

    1991-10-01

    The predominant mucins in human whole saliva, MG1 and MG2, serve to protect and to lubricate the oral cavity. In this study, both unstimulated and stimulated whole salivas were collected from two groups of subjects: young (18-35 years of age) and aged (65-83 years of age). The subjects were in apparent good health. Saliva samples from each subject were analyzed by SDS-PAGE. The gels were stained with Stains-all, and both MG1 and MG2 were quantitated by video-image densitometry. The protocol gave reproducible values for each mucin. The stimulated and unstimulated salivas from aged subjects showed significant reductions in concentrations of both MG1 and MG2, as quantitated in mucin dye-binding units. Possible associations of these reductions with the aging process are discussed. PMID:1719051

  4. Age-related changes in mucins from human whole saliva.

    PubMed

    Denny, P C; Denny, P A; Klauser, D K; Hong, S H; Navazesh, M; Tabak, L A

    1991-10-01

    The predominant mucins in human whole saliva, MG1 and MG2, serve to protect and to lubricate the oral cavity. In this study, both unstimulated and stimulated whole salivas were collected from two groups of subjects: young (18-35 years of age) and aged (65-83 years of age). The subjects were in apparent good health. Saliva samples from each subject were analyzed by SDS-PAGE. The gels were stained with Stains-all, and both MG1 and MG2 were quantitated by video-image densitometry. The protocol gave reproducible values for each mucin. The stimulated and unstimulated salivas from aged subjects showed significant reductions in concentrations of both MG1 and MG2, as quantitated in mucin dye-binding units. Possible associations of these reductions with the aging process are discussed.

  5. 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.

  6. Protective effects of Semiaquilegia adoxoides n-butanol extract against hydrogen peroxide-induced oxidative stress in human lens epithelial cells.

    PubMed

    Liang, Bing; Wei, Wei; Wang, Jianta; Zhang, Mingming; Xu, Ran; Wu, Fei; Xiao, Haitao; Tang, Lei

    2016-09-01

    Context Hydrogen peroxide (H2O2)-induced damage in the lens epithelium leads to cell death and cataract. Semiaquilegia adoxoides (DC.) Makino (Ranunculaceae), a folk medicine of Hmong (an ethnic group of China), has been traditionally used to treat cataract; however, the underlying molecular mechanism is yet to be uncovered. Objective This study aimed to investigate whether the n-butanol extract of S. adoxoides (nSA) is effective against the H2O2-induced oxidative stress in human lens epithelial (HLE) cells. Materials and methods Human lens epithelial (SRA 01/04) cells were stimulated by H2O2 (250 μM) in the presence or absence of nSA. The antioxidant effects of nSA were determined in terms of cell viability (MTT assay), apoptosis (AnnexinV/PI staining), radical scavenging capability (various enzymatic assays), loss of mitochondrial membrane potential (Rhodamine 123 staining), expression of apoptotic markers including caspase-3 and caspase-9 and the change of Bcl-2/Bax ratio (western blot) in the HLE cells. Results The results showed that pretreatment of nSA (250, 500 and 1000 μg/mL) markedly reduced H2O2-induced cellular apoptosis and malondialdehyde accumulation, but elevated the activities of total superoxide dismutase, catalase, glutathione peroxidase. Thus, the total antioxidative capability was enhanced upon the nSA treatment meanwhile the loss of mitochondrial membrane potential was prevented. Moreover, nSA at concentrations of 250, 500 and 1000 μg/mL also significantly suppressed the activation of caspase-3 and -9, and increased the Bcl-2/Bax ratio in the HLE cells. Discussion and conclusion Our findings suggested that nSA is a potential prophylactic agent in the prevention of cataractogeneis.

  7. 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.

  8. 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

  9. 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

    2016-01-01

    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.

  10. Age-dependent fatigue behaviour of human cortical bone.

    PubMed

    Diab, T; Sit, S; Kim, D; Rho, J; Vashishth, D

    2005-01-01

    Despite a general understanding that bone quality contributes to skeletal fragility, very little information exits on the age-dependent fatigue behavior of human bone. In this study four-point bending fatigue tests were conducted on aging bone in conjunction with the analysis of stiffness loss and preliminary investigation of nanoindentation based measurements of local tissue stiffness and histological evaluation of resultant tensile and compressive damage to identify the damage mechanism responsible for the increase in age-related bone fragility. The results obtained show that there is an exponential decrease in fatigue life with age, and old bone exhibits different modulus degradation profiles than young bone. In addition, this study provides preliminary evidence indicating that during fatigue loading, younger bone formed diffuse damage, lost local tissue stiffness on the tensile side. Older bone, in contrast, formed linear microcracks lost local tissue stiffness on the compressive side. Thus, the propensity of aging human bone to form more linear microcracks than diffuse damage may be a significant contributor to bone quality, and age related fragility in bone.

  11. Aging and the human vestibular nuclei: morphometric analysis.

    PubMed

    Alvarez, J C; Díaz, C; Suárez, C; Fernández, J A; González del Rey, C; Navarro, A; Tolivia, J

    2000-04-14

    The data concerning the effects of age on the brainstem are scarce and few works are devoted to the human vestibular nuclear complex. The study of the effects of aging in the vestibular nuclei could have clinical interest due to the high prevalence of balance control and gait problems in the elderly. We have used in this work eight human brainstems of different ages sectioned and stained by the formaldehyde-thionin technique. The neuron's profiles were drawn with a camera lucida and Abercrombie's method was used to estimate the total number of neurons. The test of Kolmogorov-Smirnov with the correction of Lilliefors was used to evaluate the fit of our data to a normal distribution and a regression analysis was done to determine if the variation of our data with age was statistically significant. Aging does not affect the volume or length of the vestibular nuclear complex. Our results clearly show that neuronal loss occurs with aging in the descending (DVN), medial (MVN), and lateral (LVN) vestibular nuclei, but not in the superior (SVN). There are changes in the proportions of neurons of different sizes but they are not statistically significant. The neuronal loss could be related with the problems that elderly people have to compensate unilateral vestibular lesions and the alterations of the vestibulospinal reflexes. The preservation of SVN neurons can explain why vestibulo-ocular reflexes are compensated after unilateral vestibular injuries.

  12. 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

  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. 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

  15. 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.

  16. 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. PMID:25902704

  17. Uniquely human self-control begins at school age.

    PubMed

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

    2015-11-01

    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 resist an impulse for immediate gratification, repeat a previously successful action, attend to a distracting noise, and quit in the face of repeated failure. Six-year-old children were more skillful than either 3-year-olds or chimpanzees at controlling their impulses. These results suggest that humans' most fundamental skills of self-control - as part of the overall decision-making process - are a part of their general great ape heritage, and that their species-unique skills of self-control begin at around the age at which many children begin formal schooling.

  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. Total body potassium in aging humans: A longitudinal study

    SciTech Connect

    Flynn, M.A.; Nolph, G.B.; Baker, A.S.; Martin, W.M.; Krause, G. )

    1989-10-01

    Total body potassium (TBK) data calculated from longitudinal measurements over 18 y of 40K by whole-body counting of 564 male and 61 female healthy humans in a 2-pi liquid scintillation counter show little change in females younger than 50 y compared with males of those ages. Males show less TBK from 41 y onward as they age, with most rapid rate of loss between 41 and 60 y. Females have a rapid loss of TBK when they are older than 60 y; the loss is at a greater rate than that of males. Percent total body fat calculated from total body weight and lean body mass (LBM) derived from TBK document greater adiposity in females at all ages except ages 51-60 y when females are similar to males in change in percent fat per year per centimeter.

  1. A network model of human aging: Limits, errors, and information

    NASA Astrophysics Data System (ADS)

    Farrell, Spencer; Mitnitski, Arnold; Rockwood, Kenneth; Rutenberg, Andrew

    The Frailty Index (FI) quantifies human aging using the fraction of accumulated age-related deficits. The FI correlates strongly with mortality and accumulates non-linearly and stochastically with age. Clinical data shows a nearly universal limit of FI <= 0 . 7 . We computationally model an aging population using a network model of interacting deficits. Deficits damage and repair at rates that depend upon the average damage of connected nodes. The model is parametrized to fit clinical data. We find that attribution errors, especially false negative, allow the model to recover the frailty limit. Mutual information allows us to assess how well the FI can predict mortality. Mutual information provides a non-parametric measure of how the FI predicts mortality. We find that attribution errors have a small effect on the mutual information when many deficits are included in the model. The mutual information of our model and of the clinical data are comparable.

  2. Effects of aging on the mechanical behavior of human dentin.

    PubMed

    Arola, D; Reprogel, R K

    2005-06-01

    An experimental study on the mechanical behavior of human dentin and the influence of age was conducted. Beams with rectangular cross-section were sectioned from the coronal dentin of virgin extracted molars (N = 76) that were obtained from (N = 70) patients between 17 and 80 years of age. The beams were loaded in either quasi-static 4-point flexure or 4-point flexural fatigue to failure and the stiffness, strength and fatigue properties were evaluated. In characterizing the fatigue response the beams were divided into two age groups that were regarded as young (17 < or = age < or = 30, mean +/- std. dev. = 25 +/- 5 years) and old (50 < or = age < or = 80, mean +/- std. dev. = 64 +/- 9 years) dentin. Results from monotonic loading showed that both the flexural strength and strain to fracture of dentin decreased significantly with age. The fatigue life of dentin increased with a reduction in cyclic stress amplitude and the fatigue strength of young dentin was greater than that of old dentin at all cyclic stress amplitudes. The endurance strength of young dentin (at 10(7) cycles) was approximately 44 MPa, whereas the old dentin exhibited an endurance strength of approximately 23 MPa. Based on differences in the mechanical behavior and microscopic features of the fracture surfaces from the young and old specimens, aging appears to result in an increase in both the rate of damage initiation and propagation in dentin.

  3. 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).

  4. Polymethoxyflavones as agents that prevent formation of cataract: nobiletin congeners show potent growth inhibitory effects in human lens epithelial cells.

    PubMed

    Miyata, Yoshiki; Oshitari, Tetsuta; Okuyama, Yuji; Shimada, Arata; Takahashi, Hideyo; Natsugari, Hideaki; Kosano, Hiroshi

    2013-01-01

    Posterior capsular opacification (PCO) is the most frequent complication and the primary reason for visual decrease after extracapsular cataract surgery. The proliferation and migration of leftover lens epithelial cells (LECs) after surgery may contribute to the development of PCO. To prevent PCO, a rational approach would be to inhibit both the proliferation and the migration of LECs using nontoxic xenobiotics. Nobiletin, one of the most abundant polymethoxyflavones (PMFs) in citrus peel, and its synthetic congeners displayed a potent inhibition of LEC proliferation. Structural features which enhance anti-proliferative activity have also been discussed.

  5. 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.

  6. 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

  7. Effects of Age and Dysfunction on Human Meibomian Glands

    PubMed Central

    Nien, Chyong Jy; Massei, Salina; Lin, Gloria; Nabavi, Cameron; Tao, Jeremiah; Brown, Donald J.; Paugh, Jerry R.; Jester, James V.

    2015-01-01

    Objective To identify age-related changes in human meibomian glands that may be associated with meibomian gland dysfunction (MGD). Methods Excess eyelid tissue from 36 patients (age range, 18–95 years, 19 female, 17 male) who underwent canthoplasty procedures were used. Dermatologic history, age, and presence of MGD were recorded. Samples were frozen, sectioned, and stained with specific antibodies against peroxisome proliferator–activated receptor γ(PPARγ) to identify meibocyte differentiation, Ki67 nuclear antigen to identify cycling cells, and CD45 to identify inflammatory cell infiltration. Results Staining for PPARγ showed cytoplasmic and nuclear localization in the 2 youngest subjects (ages, 18 and 44 years). Older individuals (>60 years) showed predominantly nuclear staining, with cytoplasmic staining limited to the basal acinar cells in 17 of 31 subjects. The number of Ki67 positively stained basal cells were significantly elevated in the younger compared with older subjects based on linear regression analysis (r2= 0.35; P <.001). There was also a significant correlation between MG expression grade and CD45 cell infiltration (r =0.414; P =.05). Conclusions These results indicate that aging human meibomian glands show decreased meibocyte differentiation and cell cycling that is associated with the development of MGD. Findings also suggest that altered PPARγ signaling may lead to acinar atrophy and development of an age-related hyposecretory MGD. Clinical Relevance Meibomian gland dysfunction and evaporative dry eye are common age-related eyelid disorders. Understanding the underlying mechanism of MGD may lead to the development of novel therapeutic strategies to treat this disease. PMID:21482872

  8. 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.

  9. Aquaporin-1 down regulation associated with inhibiting cell viability and inducing apoptosis of human lens epithelial cells

    PubMed Central

    Zheng, Hong-Hua; Xu, Guo-Xing; Guo, Jian; Fu, Li-Cheng; Yao, Yao

    2016-01-01

    AIM To investigate the role of Aquaporin-1 (AQP-1) in lens epithelial cells (LECs) and its potential target genes. AQP-1 is specifically expressed in LECs of eyes and is significant for lens homeostasis and transparency maintenance. Herein, AQP-1 expression in LECs was investigated to evaluate its influence on cell survival in association with its potential role in cataract formation. METHODS LECs were transfected with lentivirus carrying AQP-1 small interfering RNA (siRNA). Real-time polymerase chain reaction (PCR) and Western blotting were conducted to detect AQP-1 expression in LECs from different groups. Meanwhile, cell counting kit-8 (CCK-8) assay and flow cytometry were performed to measure LEC proliferation and apoptosis, respectively. RESULTS AQP-1 expression was significantly reduced in LECs, both at mRNA and protein levels (P<0.05), after siRNA treatment. Decreased cell viability was detected by CCK-8 assay in LECs with siRNA interference, compared to control cells (P<0.05). The apoptosis rate significantly increased in cells after siRNA interference (P<0.05). CONCLUSION The decreased cell viability following AQP-1 down regulation is largely due to its induction of apoptosis of LECs. AQP-1 reduction might lead to changes of physiological functions in LECs, which might be associated with the occurrence and development of cataracts. PMID:26949604

  10. Human Ageing Genomic Resources: Integrated databases and tools for the biology and genetics of ageing

    PubMed Central

    Tacutu, Robi; Craig, Thomas; Budovsky, Arie; Wuttke, Daniel; Lehmann, Gilad; Taranukha, Dmitri; Costa, Joana; Fraifeld, Vadim E.; de Magalhães, João Pedro

    2013-01-01

    The Human Ageing Genomic Resources (HAGR, http://genomics.senescence.info) is a freely available online collection of research databases and tools for the biology and genetics of ageing. HAGR features now several databases with high-quality manually curated data: (i) GenAge, a database of genes associated with ageing in humans and model organisms; (ii) AnAge, an extensive collection of longevity records and complementary traits for >4000 vertebrate species; and (iii) GenDR, a newly incorporated database, containing both gene mutations that interfere with dietary restriction-mediated lifespan extension and consistent gene expression changes induced by dietary restriction. Since its creation about 10 years ago, major efforts have been undertaken to maintain the quality of data in HAGR, while further continuing to develop, improve and extend it. This article briefly describes the content of HAGR and details the major updates since its previous publications, in terms of both structure and content. The completely redesigned interface, more intuitive and more integrative of HAGR resources, is also presented. Altogether, we hope that through its improvements, the current version of HAGR will continue to provide users with the most comprehensive and accessible resources available today in the field of biogerontology. PMID:23193293

  11. Human Ageing Genomic Resources: integrated databases and tools for the biology and genetics of ageing.

    PubMed

    Tacutu, Robi; Craig, Thomas; Budovsky, Arie; Wuttke, Daniel; Lehmann, Gilad; Taranukha, Dmitri; Costa, Joana; Fraifeld, Vadim E; de Magalhães, João Pedro

    2013-01-01

    The Human Ageing Genomic Resources (HAGR, http://genomics.senescence.info) is a freely available online collection of research databases and tools for the biology and genetics of ageing. HAGR features now several databases with high-quality manually curated data: (i) GenAge, a database of genes associated with ageing in humans and model organisms; (ii) AnAge, an extensive collection of longevity records and complementary traits for >4000 vertebrate species; and (iii) GenDR, a newly incorporated database, containing both gene mutations that interfere with dietary restriction-mediated lifespan extension and consistent gene expression changes induced by dietary restriction. Since its creation about 10 years ago, major efforts have been undertaken to maintain the quality of data in HAGR, while further continuing to develop, improve and extend it. This article briefly describes the content of HAGR and details the major updates since its previous publications, in terms of both structure and content. The completely redesigned interface, more intuitive and more integrative of HAGR resources, is also presented. Altogether, we hope that through its improvements, the current version of HAGR will continue to provide users with the most comprehensive and accessible resources available today in the field of biogerontology.

  12. [Histological study on aging changes in the human tongue].

    PubMed

    Nakayama, M

    1991-04-01

    Dryness of the mouth, taste disturbance or misswallowing may appear due to physiological changes of tongue especially in old aged person. The purpose of this study is to investigate histological changes related to aging in the human tongue, qualitatively and quantitatively. The samples were collected from 100 autopsy-cases without any pathological changes consisting of 50 males and 50 females aged between 5 and 82. Five specimens (I-V) were obtained from each tongue by frontal section. Specimen I (anterior part of tongue), III (central part), V (posterior part) were studied. Each specimen with thickness of 4 microns were stained with Hematoxylin-Eosin and Alucian-Blue. Tongue mucosa, glands such as Blandin-Nuhn gland, von Ebner gland and those glands distributed in the root of tongue, and M. longitudinalis superior were observed histologically. The study was done quantitatively by I-BAS one picture analyzer manufactured by Zeiss Co. The results of this study are as following: 1) The epithelium of lingual mucosa The thickness of epithelium decreased with aging, rather prominent on dorsal part than the lateral. 2) lingual glands Acinar atrophy increased with aging, especially quickly in females. The atrophy of the acinus started from 40 years old in Blandin-nuhn gland and 30 in von Ebner gland. However, tongue root glandular atrophy was milder in comparison with the other two glands. 3) Lingual muscles Decrease in muscle fiber diameter with aging is also observed.

  13. 21 CFR 886.4300 - Intraocular lens guide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Intraocular lens guide. 886.4300 Section 886.4300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4300 Intraocular lens guide. (a) Identification. An intraocular lens guide is a device...

  14. Aging of Non-Visual Spectral Sensitivity to Light in Humans: Compensatory Mechanisms?

    PubMed Central

    Najjar, Raymond P.; Chiquet, Christophe; Teikari, Petteri; Cornut, Pierre-Loïc; Claustrat, Bruno; Denis, Philippe; Gronfier, Claude

    2014-01-01

    The deterioration of sleep in the older population is a prevalent feature that contributes to a decrease in quality of life. Inappropriate entrainment of the circadian clock by light is considered to contribute to the alteration of sleep structure and circadian rhythms in the elderly. The present study investigates the effects of aging on non-visual spectral sensitivity to light and tests the hypothesis that circadian disturbances are related to a decreased light transmittance. In a within-subject design, eight aged and five young subjects were exposed at night to 60 minute monochromatic light stimulations at 9 different wavelengths (420–620 nm). Individual sensitivity spectra were derived from measures of melatonin suppression. Lens density was assessed using a validated psychophysical technique. Although lens transmittance was decreased for short wavelength light in the older participants, melatonin suppression was not reduced. Peak of non-visual sensitivity was, however, shifted to longer wavelengths in the aged participants (494 nm) compared to young (484 nm). Our results indicate that increased lens filtering does not necessarily lead to a decreased non-visual sensitivity to light. The lack of age-related decrease in non-visual sensitivity to light may involve as yet undefined adaptive mechanisms. PMID:24465738

  15. Age-related changes in human vitreous structure.

    PubMed

    Sebag, J

    1987-01-01

    Changes in vitreous structure that occur with aging are important in the pathogenesis of vitreous liquefaction (synchisis senilis), vitreous detachment, and retinal disease. Vitreous morphology was studied in 59 human eyes post-mortem using dark-field horizontal slit illumination of the entire dissected vitreous. In many individuals younger than 30 years, the vitreous was homogeneous in structure. Middle-aged individuals had macroscopic fibers in the central vitreous, which coursed anteroposteriorly and inserted into the vitreous base and the vitreous cortex, posteriorly. During senescence, the vitreous volume was reduced, the vitreous body was collapsed (syneresis), and the fibers were thickened, tortuous, and surrounded by liquid vitreous. This sequence of age-related changes probably results from a progressive reorganization of the hyaluronic acid and collagen molecular networks. Characterization of the molecular events underlying these changes will elucidate the mechanisms of the phenomena of synchisis, syneresis, and detachment, and may provide methods with which to prevent or induce vitreous detachment prophylactically.

  16. Human mortality at very advanced age might be constant.

    PubMed

    Klemera, P; Doubal, S

    1997-11-01

    An attempt was made to identify the course of the mortality rate at the upper tail of human age. The only known data suitable for this purpose were published by Riggs and Millecchia (J.E. Riggs, R.J. Millecchia, Mech. Ageing Dev. 62 (1992) 191-199) and our analysis follows up their results. By means of mathematical elaboration it was proved that these data imply a constant mortality rate (approx. 25% per year) at ages above 113 years for men and above 116 years for women. Indirect arguments supporting the validity of the source data are discussed. Nevertheless, even if the source data are mistaken, we proved they cannot be the product of purely random errors and our results may contribute to the elucidation of the origin of those systematic errors. PMID:9379712

  17. 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

  18. Does infrared or ultraviolet light damage the lens?

    PubMed

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

    2016-02-01

    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.

  19. Telocytes and putative stem cells in ageing human heart

    PubMed Central

    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 http://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 mm2) 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). PMID:25545142

  20. Vasodilatory responsiveness to adenosine triphosphate in ageing humans

    PubMed Central

    Kirby, Brett S; Crecelius, Anne R; Voyles, Wyatt F; Dinenno, Frank A

    2010-01-01

    Endothelium-dependent vasodilatation is reduced with advancing age in humans, as evidenced by blunted vasodilator responsiveness to acetylcholine (ACh). Circulating adenosine triphosphate (ATP) has been implicated in the control of skeletal muscle vascular tone during mismatches in oxygen delivery and demand (e.g. exercise) via binding to purinergic receptors (P2Y) on the endothelium evoking subsequent vasodilatation, and ageing is typically associated with reductions in muscle blood flow under such conditions. Therefore, we tested the hypothesis that ATP-mediated vasodilatation is impaired with age in healthy humans. We measured forearm blood flow (venous occlusion plethysmography) and calculated vascular conductance (FVC) responses to local intra-arterial infusions of ACh, ATP, and sodium nitroprusside (SNP) before and during ascorbic acid (AA) infusion in 13 young and 13 older adults. The peak increase in FVC to ACh was significantly impaired in older compared with young adults (262 ± 71%vs. 618 ± 97%; P < 0.05), and this difference was abolished during AA infusion (510 ± 82%vs. 556 ± 71%; not significant, NS). In contrast, peak FVC responses were not different between older and young adults to either ATP (675 ± 105%vs. 734 ± 126%) or SNP (1116 ± 111%vs. 1138 ± 148%) and AA infusion did not alter these responses in either age group (both NS). In another group of six young and six older adults, we determined whether vasodilator responses to adenosine and ATP were influenced by P1-receptor blockade via aminophylline. The peak FVC responses to adenosine were not different in young (350 ± 65%) versus older adults (360 ± 80%), and aminophylline blunted these responses by ∼50% in both groups. The peak FVC responses to ATP were again not different in young and older adults, and aminophylline did not impact the vasodilatation in either group. Thus, in contrast to the observed impairments in ACh responses, the vasodilatory response to exogenous ATP is not

  1. 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 ...

  2. Contact Lens Solution Toxicity

    MedlinePlus

    ... rash and rashes clinical tools newsletter | contact Share | Contact Lens Solution Toxicity Information for adults A A A This image shows a reaction to contact lens solution. The prominent blood vessels and redness ...

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

    PubMed

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

    2015-09-01

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

  4. 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

  5. Spatial distribution of the human enamel fracture toughness with aging.

    PubMed

    Zheng, Qinghua; Xu, Haiping; Song, Fan; Zhang, Lan; Zhou, Xuedong; Shao, Yingfeng; Huang, Dingming

    2013-10-01

    A better understanding of the fracture toughness (KIC) of human enamel and the changes induced by aging is important for the clinical treatment of teeth cracks and fractures. We conducted microindentation tests and chemical content measurements on molar teeth from "young" (18 ≤ age ≤ 25) and "old" (55 ≤ age) patients. The KIC and the mineral contents (calcium and phosphorus) in the outer, the middle, and the inner enamel layers within the cuspal and the intercuspal regions of the crown were measured through the Vickers toughness test and Energy Dispersive X-Ray Spectroscopy (EDS), respectively. The elastic modulus used for the KIC calculation was measured through atomic force microscope (AFM)-based nanoindentation tests. In the outer enamel layer, two direction-specific values of the KIC were calculated separately (direction I, crack running parallel to the occlusal surface; direction II, perpendicular to direction I). The mean KIC of the outer enamel layer was lower than that of the internal layers (p<0.05). No other region-related differences in the mechanical properties were found in both groups. In the outer enamel layer, old enamel has a lower KIC, II and higher mineral contents than young enamel (p<0.05). The enamel surface becomes more prone to cracks with aging partly due to the reduction in the interprismatic organic matrix observed with the maturation of enamel.

  6. Age-dependent motor unit remodelling in human limb muscles.

    PubMed

    Piasecki, Mathew; Ireland, Alex; Jones, David A; McPhee, Jamie S

    2016-06-01

    Voluntary control of skeletal muscle enables humans to interact with and manipulate the environment. Lower muscle mass, weakness and poor coordination are common complaints in older age and reduce physical capabilities. Attention has focused on ways of maintaining muscle size and strength by exercise, diet or hormone replacement. Without appropriate neural innervation, however, muscle cannot function. Emerging evidence points to a neural basis of muscle loss. Motor unit number estimates indicate that by age around 71 years, healthy older people have around 40 % fewer motor units. The surviving low- and moderate-threshold motor units recruited for moderate intensity contractions are enlarged by around 50 % and show increased fibre density, presumably due to collateral reinnervation of denervated fibres. Motor unit potentials show increased complexity and the stability of neuromuscular junction transmissions is decreased. The available evidence is limited by a lack of longitudinal studies, relatively small sample sizes, a tendency to examine the small peripheral muscles and relatively few investigations into the consequences of motor unit remodelling for muscle size and control of movements in older age. Loss of motor neurons and remodelling of surviving motor units constitutes the major change in ageing muscles and probably contributes to muscle loss and functional impairments. The deterioration and remodelling of motor units likely imposes constraints on the way in which the central nervous system controls movements. PMID:26667009

  7. 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.

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

    PubMed

    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.

  9. Replicative senescence: the human fibroblast comes of age.

    PubMed

    Goldstein, S

    1990-09-01

    Human diploid fibroblasts undergo replicative senescence predominantly because of arrest at the G1/S boundary of the cell cycle. Senescent arrest resembles a process of terminal differentiation that appears to involve repression of proliferation-promoting genes with reciprocal new expression of antiproliferative genes, although post-transcriptional factors may also be involved. Identification of participating genes and clarification of their mechanisms of action will help to elucidate the universal cellular decline of biological aging and an important obverse manifestation, the rare escape of cells from senescence leading to immortalization and oncogenesis.

  10. Human stem cells as targets for the aging and diseases of aging processes.

    PubMed

    Trosko, James E

    2003-03-01

    While many theories have been proposed for the aging process, and many debates on the matter of aging and the diseases of aging being either the result of the same or independent processes, most have not considered humans as a hierarchical system made up of cybernetically interacting levels of organization. To understand the aging process and the diseases of aging, one must view the human as the result of the total genomic DNA in the single fertilized egg that proliferates, differentiates and develops into an individual of about 100 trillion cells, organized by different cell types (pluri-potent stem cells, progenitor stem cells, terminally differentiated cells) into multiple tissue, organ and organ systems which interact with each other via endogenous factors and with exogenous factors. Our hypothesis is that both aging and diseases of aging are dependent of the normal functioning of the pluri-potent stem cell pool. Specifically, the concept involves the cybernetic feedback between the 'quantity' of the stem cell pool in each tissue niche with the 'quality' of the stem cells in the pool. The process of gap junctional inter-cellular communication (GJIC), which has been implicated in the evolution from the single cell organism to the multi-cellular organisms, requiring growth control, differentiation, apoptosis, adaptive response capability of differentiated cells and senescence, is speculated to be a shared mechanism in stem cell biology and in many chronic disease processes (teratogenesis; carcinogenesis, atherogenesis, diabetigenesis, etc.). Specifically, stem cells are assumed to be 'immortal' until induced to express their connexin genes and have functional GJIC, at which time they can differentiate and become 'mortal'. As long as the stem cells are communicating with their differentiated daughters via some extra-cellular soluble negative growth factor, the homeostatic control of their growth and differentiation is maintained for the organism. However, if the

  11. 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

  12. 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

  13. Sympathetic activity during passive heat stress in healthy aged humans

    PubMed Central

    Gagnon, Daniel; Schlader, Zachary J; Crandall, Craig G

    2015-01-01

    Abstract Cardiovascular adjustments during heat stress are generally attenuated in healthy aged humans, which could be due to lower increases in sympathetic activity compared to the young. We compared muscle sympathetic nerve activity (MSNA) between 11 young (Y: 28 ± 4 years) and 10 aged (A: 70 ± 5 years) subjects prior to and during passive heating. Furthermore, MSNA responses were compared when a cold pressor test (CPT) and lower body negative pressure (LBNP) were superimposed upon heating. Baseline MSNA burst frequency (Y: 15 ± 4 vs. A: 31 ± 3 bursts min−1, P ≤ 0.01) and burst incidence (Y: 26 ± 8 vs. A: 50 ± 7 bursts (100 cardiac cycles (CC))−1, P ≤ 0.01) were greater in the aged. Heat stress increased core temperature to a similar extent in both groups (Y: +1.2 ± 0.1 vs. A: +1.2 ± 0.0°C, P = 0.99). Absolute levels of MSNA remained greater in the aged during heat stress (burst frequency: Y: 47 ± 6 vs. A: 63 ± 11 bursts min−1, P ≤ 0.01; burst incidence: Y: 48 ± 8 vs. A: 67 ± 9 bursts (100 CC)−1, P ≤ 0.01); however, the increase in both variables was similar between groups (both P ≥ 0.1). The CPT and LBNP further increased MSNA burst frequency and burst incidence, although the magnitude of increase was similar between groups (both P ≥ 0.07). These results suggest that increases in sympathetic activity during heat stress are not attenuated in healthy aged humans. Key points Cardiovascular adjustments to heat stress are attenuated in healthy aged individuals, which could contribute to their greater prevalence of heat-related illnesses and deaths during heat waves. The attenuated cardiovascular adjustments in the aged could be due to lower increases in sympathetic nerve activity during heat stress. We examined muscle sympathetic nerve activity (MSNA) and plasma catecholamine concentrations in healthy young and aged individuals during whole-body passive heat stress. The main finding

  14. In-vivo measurements of optical properties of the ocular lens

    NASA Astrophysics Data System (ADS)

    Zuclich, Joseph A.

    1994-07-01

    `Optical aging' of the lens of the eye results from the cumulative photochemical effects of ambient light exposures and may be exacerbated by any number of disease processes and exogenous agents including acute or chronic exposure to above- ambient levels of ultraviolet and/or blue light. This `optical aging' of the lens is manifested by increased scattering of visible light, increased absorption of short-visible wavelengths, and increased fluorescence emitted at short- to mid-visible wavelengths when irradiated with UV or blue light. With age and with or without exacerbating factors, the initially clear lens takes on an increasingly yellowish and ultimately brunescent coloration associated with cortical cataract. We conducted in vivo measurements of the lens fluorescence induced by UV and blue wavelengths. The fluorescence intensity was quantitated as a function of intensity of exciting light and excitation wavelength. It was shown that other `safe' blue laser exposures induced enough of a fluorescent veiling glare to imply interference with visual function. The visual deficit was objectively demonstrated by monitoring visual evoked potential amplitudes while subjects were irradiated with blue laser light. A related study demonstrated the utility of a prototype optical biopsy instrument as a diagnostic tool for assessing the optical properties of the lens. Optical signatures of individual lenses were characterized by compiling the backscatter and fluorescence spectra elicited by each of several exciting wavelengths. By examining the optical signatures of a population of approximately 100 human lenses, several metrics were chosen for gauging the optical quality of a given lens relative to the norm for the subject's chronological age. These metrics may serve to identify cases of accelerated `optical aging' and provide early evidence of cataract or other disease processes.

  15. 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

  16. 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).

  17. 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

  18. 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.

  19. Gut Bifidobacteria Populations in Human Health and Aging

    PubMed Central

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

    2016-01-01

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

  20. 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

  1. 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. PMID:27594848

  2. Aging of microstructural compartments in human compact bone

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

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

    PubMed

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

    2013-04-01

    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.

  4. Rejuvenation of senescent cells-the road to postponing human aging and age-related disease?

    PubMed

    Sikora, Ewa

    2013-07-01

    Cellular senescence is the state of permanent inhibition of cell proliferation. Replicative senescence occurs due to the end replication problem and shortening telomeres with each cell division leading to DNA damage response (DDR). The number of short telomeres increases with age and age-related pathologies. Stress induced senescence, although not accompanied by attrition of telomeres, is also attributed to the DDR induced by irreparable DNA lesions in telomeric DNA. Senescent cells characterized by the presence of γH2AX, the common marker of double DNA strand breaks, and other senescence markers including activity of SA-β-gal, accumulate in tissues of aged animals and humans as well as at sites of pathology. It is believed that cellular senescence evolved as a cancer barrier since non-proliferating senescent cells cannot be transformed to neoplastic cells. On the other hand senescent cells favor cancer development, just like other age-related pathologies, by creating a low grade inflammatory state due to senescence associated secretory phenotype (SASP). Reversal/inhibition of cellular senescence could prolong healthy life span, thus many attempts have been undertaken to influence cellular senescence. The two main approaches are genetic and pharmacological/nutritional modifications of cell fate. The first one concerns cell reprogramming by induced pluripotent stem cells (iPSCs), which in vitro is effective even in cells undergoing senescence, or derived from very old or progeroid patients. The second approach concerns modification of senescence signaling pathways just like TOR-induced by pharmacological or with natural agents. However, knowing that aging is unavoidable we cannot expect its elimination, but prolonging healthy life span is a goal worth serious consideration. PMID:23064316

  5. The Age-Related Orientational Changes of Human Semicircular Canals

    PubMed Central

    Lyu, Hui-Ying; Chen, Ke-Guang; Yin, Dong-Ming; Hong, Juan; Yang, Lin; Zhang, Tian-Yu; Dai, Pei-Dong

    2016-01-01

    Objectives Some changes are found in the labyrinth anatomy during postnatal development. Although the spatial orientation of semicircular canals was thought to be stable after birth, we investigated the age-related orientational changes of human semicircular canals during development. Methods We retrospectively studied the computed tomography (CT) images of both ears of 76 subjects ranged from 1 to 70 years old. They were divided into 4 groups: group A (1–6 years), group B (7–12 years), group C (13–18 years), and group D (>18 years). The anatomical landmarks of the inner ear structures were determined from CT images. Their coordinates were imported into MATLAB software for calculating the semicircular canals orientation, angles between semicircular canal planes and the jugular bulb (JB) position. Differences between age groups were analyzed using multivariate statistics. Relationships between variables were analyzed using Pearson analysis. Results The angle between the anterior semicircular canal plane and the coronal plane, and the angle between the horizontal semicircular canal plane and the coronal plane were smaller in group D than those in group A (P<0.05). The JB position, especially the anteroposterior position of right JB, correlated to the semicircular canals orientation (P<0.05). However, no statistically significant differences in the angles between ipsilateral canal planes among different age groups were found. Conclusion The semicircular canals had tendencies to tilt anteriorly simultaneously as a whole with age. The JB position correlated to the spatial arrangement of semicircular canals, especially the right JB. Our calculation method helps detect developmental and pathological changes in vestibular anatomy. PMID:27090280

  6. 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.

  7. 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.

  8. Contact Lens Wearer Demographics and Risk Behaviors for Contact Lens-Related Eye Infections--United States, 2014.

    PubMed

    Cope, Jennifer R; Collier, Sarah A; Rao, Maya M; Chalmers, Robin; Mitchell, G Lynn; Richdale, Kathryn; Wagner, Heidi; Kinoshita, Beth T; Lam, Dawn Y; Sorbara, Luigina; Zimmerman, Aaron; Yoder, Jonathan S; Beach, Michael J

    2015-08-21

    Contact lenses provide safe and effective vision correction for many Americans. However, contact lens wearers risk infection if they fail to wear, clean, disinfect, and store their contact lenses as directed. Over the past decade, CDC has investigated several multistate outbreaks of serious eye infections among contact lens wearers, including Acanthamoeba keratitis. Each investigation identified frequent contact lens hygiene-related risk behaviors among patients. To guide prevention efforts, a population-based survey was used to estimate the number of contact lens wearers aged ≥18 years in the United States. A separate online survey of contact lens wearers assessed the prevalence of contact lens hygiene-related risk behaviors. Approximately 99% of wearers reported at least one contact lens hygiene risk behavior. Nearly one third of contact lens wearers reported having experienced a previous contact lens-related red or painful eye requiring a doctor's visit. An estimated 40.9 million U.S. adults wear contact lenses, and many could be at risk for serious eye infections because of poor contact lens wear and care behaviors. These findings have informed the creation of targeted prevention messages aimed at contact lens wearers such as keeping all water away from contact lenses, discarding used disinfecting solution from the case and cleaning with fresh solution each day, and replacing their contact lens case every 3 months.

  9. Glycation by Ascorbic Acid Oxidation Products Leads to the Aggregation of Lens Proteins

    PubMed Central

    Linetsky, Mikhail; Shipova, Ekaterina; Cheng, Rongzhu; Ortwerth, Beryl J.

    2008-01-01

    Previous studies from this laboratory have shown that there are striking similarities between the yellow chromophores, fluorophores and modified amino acids released by proteolytic digestion from calf lens proteins ascorbylated in vitro and their counterparts isolated from aged and cataractous lens proteins. The studies reported in this communication were conducted to further investigate whether ascorbic acid-mediated modification of lens proteins could lead to the formation of lens protein aggregates capable of scattering visible light, similar to the high molecular aggregates found in aged human lenses. Ascorbic acid, but not glucose, fructose, ribose or erythrulose, caused the aggregation of calf lens proteins to proteins ranging from 2.2 × 106 up to 3.0 × 108 Da. This compared to proteins ranging from 1.8 × 106 up to 3.6 × 108 Da for the water-soluble (WS) proteins isolated from aged human lenses. This aggregation was likely due to the glycation of lens crystallins because [U-14C] ascorbate was incorporated into the aggregate fraction and because CNBH3, which reduces the initial Schiff base, prevented any protein aggregation. Reactions of ascorbate with purified crystallin fractions showed little or no aggregation of α-crystallin, significant aggregation of βH-crystallin, but rapid precipitation of purified βL- and γ-crystallin. The aggregation of lens proteins can be prevented by the binding of damaged crystallins to alpha-crystallin due to its chaperone activity. Depending upon the ratios between the components of the incubation mixtures, α-crystallin prevented the precipitation of the purified βL- and γ-crystallin fractions during ascorbylation. The addition of at least 20% of alpha-crystallin by weight into glycation mixtures with βL-, or γ-crystallins completely inhibited protein precipitation, and increased the amount of the high molecular weight aggregates in solution. Static and dynamic light scattering measurements of the supernatants from

  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. High Refractive Index Polysiloxane as Injectable, In Situ Curable Accommodating Intraocular Lens

    PubMed Central

    Hao, Xiaojuan; Jeffery, Justine L.; Le, Tam P.T.; McFarland, Gail; Johnson, Graham; Mulder, Roger J.; Garrett, Qian; Manns, Fabrice; Nankivil, Derek; Arrieta, Esdras; Ho, Arthur; Parel, Jean-Marie; Hughes, Timothy C.

    2012-01-01

    Functionalised siloxane macromonomers, with properties designed for application as an injectable, in situ curable accommodating intraocular lens (A-IOL), were prepared via reequilibration of a phenyl group-containing polysiloxane of very high molecular weight with octamethylcyclotetrasiloxane (D4) and 2,4,6,8-tetra(n-propyl-3-methacrylate)-2,4,6,8-tetramethylcyclotetrasiloxane (D4AM) in toluene using trifluoromethanesulfonic acid as a catalyst. Hexaethyldisiloxane was used as an end group to control the molecular weight of the polymer. The generated polymers had a consistency suitable for injection into the empty lens capsule. The polymers contained a low ratio of polymerisable groups so that, in the presence of a photo-initiator, they could be cured on demand in situ within 5 minutes under irradiation of blue light to form an intraocular lens within the lens capsule. All resulting polysiloxane soft gels had a low elastic modulus and thus should be able to restore accommodation. The pre-cure viscosity and post-cure modulus of the generated polysiloxanes were controlled by the end group and D4AM concentrations respectively in the re-equilibration reactions. The refractive index could be precisely controlled by adjusting the aromatic ratio in the polymer to suit such application as an artificial lens. Lens stretching experiments with both human and non-human primate cadaver lenses of different ages refilled with polysiloxane polymers provided a significant increase in amplitude of accommodation (up to 4 D more than that of the respective natural lens). Both in vitro cytotoxicity study using L929 cell lines and in vivo biocompatibility study in rabbit models demonstrated the non-cytotoxicity and ocular biocompatibility of the polymer. PMID:22594975

  12. 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. PMID:16905991

  13. Concord grape juice supplementation and neurocognitive function in human aging.

    PubMed

    Krikorian, Robert; Boespflug, Erin L; Fleck, David E; Stein, Amanda L; Wightman, Jolynne D; Shidler, Marcelle D; Sadat-Hossieny, Sara

    2012-06-13

    Polyphenol compounds found in berry fruits, in particular flavonoids, have been associated with health benefits including improvement in cognition and neuronal function with aging. Concord grape juice contains polyphenols, including anthocyanins and flavanols, and previous research has shown improvement in a number of human health conditions with grape juice supplementation. In the current study, older adult subjects with mild cognitive impairment consumed Concord grape juice or placebo for 16 weeks and were administered assessments of memory function and brain activation pre- and postintervention. Participants who consumed grape juice showed reduced semantic interference on memory tasks. Relatively greater activation in anterior and posterior regions of the right hemisphere was also observed with functional magnetic resonance imaging in the grape juice treated subjects. These findings provide further evidence that Concord grape juice can enhance neurocognitive function in older adults with mild memory decline. PMID:22468945

  14. Analysis of Aged Human Serum Albumin Affinity for Doxazosin.

    PubMed

    Chudzik, Mariola; Równicka-Zubik, Joanna; Pożycka, Jadwiga; Pawelczak, Bartosz; Sulkowska, Anna

    2016-01-01

    Structural changes of human serum albumin (HSA) caused by old age and coexisting diseases result in differences in the binding of doxazosin (DOX). DOX is a postsynaptic α1- adrenoreceptor antagonist used for treatment of hypertension and benign prostatic hyperplasia. In elderly people suffering from various renal or hepatic diseases the significant portion of N-form of human serum albumin (normal) is converted to A-form (aged). The differences in binding of doxazosin to N- and Aform of albumin are an important factor, which may determines therapeutic dosage and toxicity of the test drug. To indicate these differences, the technique of fluorescence spectroscopy was used. The association constant (Ka) obtained from fluorescence quenching demonstrated that doxazosin has higher affinity for AHSA than for HSA. In order to describe the cooperativity in binding process, the values of the Hill's coefficient has been analysed. For DOX-HSA system (λex 295 nm) Hill's coefficient is close to 1 and it indicates that there is a single class of binding sites. For DOX-HSA (λex 275 nm) and DOX-AHSA (λex 275 nm and λex 295 nm) systems we observed positive cooperativity (nH>1). A greater red shift of fluorescence emission maximum of AHSA than HSA in the presence of DOX was observed. This suggests that the binding of DOX to AHSA was accompanied by a stronger increase in polarity around the fluorophores in comparison to HSA. The binding interaction between DOX and HSA has been also studied by molecular docking simulation.

  15. 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

  16. Microindentation of the young porcine ocular lens.

    PubMed

    Reilly, Matthew; Ravi, Nathan

    2009-04-01

    Debate regarding the mechanisms of how the eye changes focus (accommodation) and why this ability is lost with age (presbyopia) has recently been rejoined due to the advent of surgical procedures for the correction of presbyopia. Due to inherent confounding factors in both in vivo and in vitro measurement techniques, mechanical modeling of the behavior of the ocular lens in accommodation has been attempted to settle the debate. However, a paucity of reliable mechanical property measurements has proven problematic in the development of a successful mechanical model of accommodation. Instrumented microindentation was utilized to directly measure the local elastic modulus and dynamic response at various locations in the lens. The young porcine lens exhibits a large modulus gradient with the highest modulus appearing at the center of the nucleus and exponentially decreasing with distance. The loss tangent was significantly higher in the decapsulated lens and the force waveform amplitude decreased significantly upon removal of the lens capsule. The findings indicate that localized measurements of the lens' mechanical properties are necessary to achieve accurate quantitative parameters suitable for mechanical modeling efforts. The results also indicate that the lens behaves as a crosslinked gel rather than as a collection of individual arched fiber cells.

  17. 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.

  18. Is atherosclerosis fundamental to human aging? Lessons from ancient mummies.

    PubMed

    Clarke, Emily M; Thompson, Randall C; Allam, Adel H; Wann, L Samuel; Lombardi, Guido P; Sutherland, M Linda; Sutherland, James D; Cox, Samantha L; Soliman, Muhammad Al-Tohamy; Abd el-Maksoud, Gomaa; Badr, Ibrahem; Miyamoto, Michael I; Frohlich, Bruno; Nur el-din, Abdel-Halim; Stewart, Alexandre F R; Narula, Jagat; Zink, Albert R; Finch, Caleb E; Michalik, David E; Thomas, Gregory S

    2014-05-01

    Case reports from Johan Czermak, Marc Ruffer, and others a century or more ago demonstrated ancient Egyptians had atherosclerosis three millennia ago. The Horus study team extended their findings, demonstrating that atherosclerosis was prevalent among 76 ancient Egyptian mummies and among 61 mummies from each of the ancient cultures of Peru, the American Southwest, and the Aleutian Islands. These findings challenge the assumption that atherosclerosis is a modern disease caused by present day risk factors. An extensive autopsy of an ancient Egyptian teenage male weaver named Nakht found that he was infected with four parasites: Schistosoma haematobium, Taenia species, Trichinella spiralis, and Plasmodium falciparum. Modern day patients with chronic inflammatory disease such as rheumatoid arthritis, systemic lupus erythematosus, and human immunodeficiency virus experience premature atherosclerosis. Could the burden of chronic inflammatory disease have been a risk factor for atherosclerosis in these ancient cultures? The prevalence of atherosclerosis in four diverse ancient cultures is consistent with atherosclerosis being fundamental to aging. The impact of risk factors in modern times, and potentially in ancient times, suggests a strong gene-environmental interplay: human genes provide a vulnerability to atherosclerosis, the environment determines when and if atherosclerosis becomes manifest clinically.

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

    PubMed

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

    2015-03-01

    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.

  20. Application of high-performance liquid chromatography combined with ultra-sensitive thermal lens spectrometric detection for simultaneous biliverdin and bilirubin assessment at trace levels in human serum.

    PubMed

    Martelanc, Mitja; Žiberna, Lovro; Passamonti, Sabina; Franko, Mladen

    2016-07-01

    We present the applicability of a new ultra-sensitive analytical method for the simultaneous determination of biliverdin and bilirubin in human serum. The method comprises isocratic reversed-phase (RP) C18 high-performance liquid chromatography (HPLC) and thermal lens spectrometric detection (TLS) based on excitation by a krypton laser emission line at 407nm. This method enables the separation of IX-α biliverdin and IX-α bilirubin in 11min with limit of detection (LOD) and limit of quantitation (LOQ) for biliverdin of 1.2nM and 3nM, and 1nM and 2.8nM for bilirubin, respectively. In addition, a step-gradient elution was set up, by changing the mobile phase composition, in order to further enhance the sensitivity for bilirubin determination with LOD and LOQ of 0.5nM and 1.5nM, respectively. In parallel, an isocratic HPLC-DAD method was developed for benchmarking against HPLC-TLS methods. The LOD and LOQ for biliverdin were 6nM and 18nM, and 2.5nM and 8nM for bilirubin, respectively. Additionally, both isocratic methods were applied for measuring biliverdin and free bilirubin in human serum samples (from 2 male and 2 female healthy donors). Combining isocratic HPLC method with TLS detector was crucial for first ever biliverdin determination in serum together with simultaneous free bilirubin determination. We showed for the first time the concentration ratio of free bilirubin versus unbound biliverdin in human serum samples.

  1. Application of high-performance liquid chromatography combined with ultra-sensitive thermal lens spectrometric detection for simultaneous biliverdin and bilirubin assessment at trace levels in human serum.

    PubMed

    Martelanc, Mitja; Žiberna, Lovro; Passamonti, Sabina; Franko, Mladen

    2016-07-01

    We present the applicability of a new ultra-sensitive analytical method for the simultaneous determination of biliverdin and bilirubin in human serum. The method comprises isocratic reversed-phase (RP) C18 high-performance liquid chromatography (HPLC) and thermal lens spectrometric detection (TLS) based on excitation by a krypton laser emission line at 407nm. This method enables the separation of IX-α biliverdin and IX-α bilirubin in 11min with limit of detection (LOD) and limit of quantitation (LOQ) for biliverdin of 1.2nM and 3nM, and 1nM and 2.8nM for bilirubin, respectively. In addition, a step-gradient elution was set up, by changing the mobile phase composition, in order to further enhance the sensitivity for bilirubin determination with LOD and LOQ of 0.5nM and 1.5nM, respectively. In parallel, an isocratic HPLC-DAD method was developed for benchmarking against HPLC-TLS methods. The LOD and LOQ for biliverdin were 6nM and 18nM, and 2.5nM and 8nM for bilirubin, respectively. Additionally, both isocratic methods were applied for measuring biliverdin and free bilirubin in human serum samples (from 2 male and 2 female healthy donors). Combining isocratic HPLC method with TLS detector was crucial for first ever biliverdin determination in serum together with simultaneous free bilirubin determination. We showed for the first time the concentration ratio of free bilirubin versus unbound biliverdin in human serum samples. PMID:27154653

  2. 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

  3. Disentangling the genetic determinants of human aging: biological age as an alternative to the use of survival measures.

    PubMed

    Karasik, David; Demissie, Serkalem; Cupples, L Adrienne; Kiel, Douglas P

    2005-05-01

    The choice of a phenotype is critical for the study of a complex genetically regulated process, such as aging. To date, most of the twin and family studies have focused on broad survival measures, primarily age at death or exceptional longevity. However, on the basis of recent studies of twins and families, biological age has also been shown to have a strong genetic component, with heritability estimates ranging from 27% to 57%. The aim of this review is twofold: first, to summarize growing consensus on reliable methods of biological age assessment, and second, to demonstrate validity of this phenotype for research in the genetics of aging in humans.

  4. 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

  5. A transcriptional profile of aging in the human kidney.

    PubMed

    Rodwell, Graham E J; Sonu, Rebecca; Zahn, Jacob M; Lund, James; Wilhelmy, Julie; Wang, Lingli; Xiao, Wenzhong; Mindrinos, Michael; Crane, Emily; Segal, Eran; Myers, Bryan D; Brooks, James D; Davis, Ronald W; Higgins, John; Owen, Art B; Kim, Stuart K

    2004-12-01

    In this study, we found 985 genes that change expression in the cortex and the medulla of the kidney with age. Some of the genes whose transcripts increase in abundance with age are known to be specifically expressed in immune cells, suggesting that immune surveillance or inflammation increases with age. The age-regulated genes show a similar aging profile in the cortex and the medulla, suggesting a common underlying mechanism for aging. Expression profiles of these age-regulated genes mark not only age, but also the relative health and physiology of the kidney in older individuals. Finally, the set of aging-regulated kidney genes suggests specific mechanisms and pathways that may play a role in kidney degeneration with age.

  6. A Transcriptional Profile of Aging in the Human Kidney

    PubMed Central

    2004-01-01

    In this study, we found 985 genes that change expression in the cortex and the medulla of the kidney with age. Some of the genes whose transcripts increase in abundance with age are known to be specifically expressed in immune cells, suggesting that immune surveillance or inflammation increases with age. The age-regulated genes show a similar aging profile in the cortex and the medulla, suggesting a common underlying mechanism for aging. Expression profiles of these age-regulated genes mark not only age, but also the relative health and physiology of the kidney in older individuals. Finally, the set of aging-regulated kidney genes suggests specific mechanisms and pathways that may play a role in kidney degeneration with age. PMID:15562319

  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. Role of Mineralocorticoid Receptors in Arterial Stiffness in Human Aging

    PubMed Central

    Hwang, Moon-Hyon; Yoo, Jeung-Ki; Luttrell, Meredith; Kim, Han-Kyul; Meade, Thomas H.; English, Mark; Nichols, Wilmer W.; Christou, Demetra D.

    2013-01-01

    Arterial stiffness, an independent predictor of cardiovascular disease, is increased in aging, but the underlying mechanisms are not completely understood. Mineralocorticoid receptors (MR) may contribute to oxidative stress and arterial stiffness in healthy older adults. To test the hypothesis that short-term MR blockade may reduce oxidative stress and improve arterial stiffness, we conducted a randomized, double blind, crossover study using the selective MR blocker Eplerenone or placebo in 23 older adults (age, 64±1 years; mean±SE) free from overt cardiovascular and other clinical disease (e.g, diabetes, renal and liver disease). In response to MR blockade, brachial and carotid blood pressure decreased (P≤0.01). However, MR blockade had no effect on oxidative stress (oxidized LDL, 61.2±6.8 vs. 62.4±7.4 U/L, P=0.9; placebo vs. Eplerenone) and arterial stiffness (aortic pulse wave velocity (PWV), 9.17±1.19 vs. 8.92±1.19 m/sec, P=0.5; leg PWV, 13.45±0.45 vs. 12.81±0.47 m/sec, P=0.3; arm PWV, 11.43±0.62 vs. 11.73±0.68 m/sec, P=0.7; carotid artery compliance, 0.150±0.013 vs. 0.149±0.014 mm2/mmHg, P=0.8; distensibility, 23.1±1.8 vs. 23.3±1.7 10−3/kPa, P=0.8; β stiffness index, 3.5±0.3 vs. 3.6±0.3, P=0.6; and augmentation index, 16.0±2.2 vs. 15.6±2.8 %, P=0.8). These results provide the first evidence that MR do not appear to contribute to oxidative stress in human aging and that short-term MR blockade does not result in reduced oxidative stress and improved arterial stiffness. PMID:23707930

  9. Refractive Index Measurement of the Isolated Crystalline Lens Using Optical Coherence Tomography

    PubMed Central

    Uhlhorn, Stephen R.; Borja, David; Manns, Fabrice; Parel, Jean-Marie

    2008-01-01

    An optical coherence tomography system has been developed that was designed specifically for imaging the isolated crystalline lens. Cross-sectional OCT images were recorded on 40 lenses from 32 human donors with an age range of 6 – 82 years. A method has been developed to measure the axial thickness and average refractive index of the lens from a single recorded image. The measured average group refractive index at the measurement wavelength of 825 nm was converted to the average phase refractive index at 589 nm using lens dispersion data from the literature. The average refractive index for all lenses measured was 1.408 ± 0.005 which agrees well with recent MRI measurements of the lens index gradient. A linear regression of the data resulted in a statistically significant decrease in the average refractive index with age, but a simple linear model was insufficient to explain the age dependence. The results presented here suggest that the peak refractive index in the nucleus is closer to 1.420, rather than the previously accepted value of 1.406. PMID:18824191

  10. Age-related changes in deformability of human erythrocytes.

    PubMed

    Sutera, S P; Gardner, R A; Boylan, C W; Carroll, G L; Chang, K C; Marvel, J S; Kilo, C; Gonen, B; Williamson, J R

    1985-02-01

    The present study was designed to further the characterization of age-related changes in the deformability of human erythrocytes. The top (approximately young) and bottom (approximately old) 10% fractions of density-separated red cells from ten normal donors were subjected to graded levels of shear stress in a rheoscope. Measurements were made of steady-state elongation (cells tank treading in a state of dynamic equilibrium) and the time course of shape recovery following abrupt cessation of shear. In parallel with the rheologic experiments, several physical and chemical properties were assayed to determine correlates of mechanical properties. These included mean cell volume, mean corpuscular hemoglobin concentration, type A1 hemoglobin, glucosylation of membrane proteins, and membrane phospholipid and protein concentration. The microrheologic observations revealed that only about 90% of the old cells retained their capacity to tank tread. However, the tank-treading cells elongated less than their younger counterparts at corresponding levels of shear stress, thus demonstrating a reduced level of deformability. Further analysis of the data indicates that increases in membrane viscosity and elastic modulus along with a significant loss in excess surface area contribute to the limitation of the ability of the older cells to change shape.

  11. 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.

  12. 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

  13. 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.

  14. A Novel Peptide Hydrogel for an Antimicrobial Bandage Contact Lens.

    PubMed

    Gallagher, Andrew G; Alorabi, Jamal A; Wellings, Donald A; Lace, Rebecca; Horsburgh, Mal J; Williams, Rachel L

    2016-08-01

    A peptide hydrogel with an antimicrobial activity is developed as a bandage contact lens. The antimicrobial activity is enhanced with the addition of the biomolecules penicillin G or poly-ε-lysine and is positive against Staphylococcus aureus and Escherichia coli. The lens is also noncytotoxic toward a human corneal epithelial cell line and as a consequence is of great potential as a drug-eluting bandage lens replacing conventional corneal ulcer treatment. PMID:27276231

  15. 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...

  16. Extraction, purification and characterization of the crystallin protein of cataractous eye lens nucleus.

    PubMed

    Sher, Muhammad; Hameed, Ayesha; Noreen, Sobia; Fayyaz-ur-Rehman, Muhammad; Hussain, Muhammad Ajaz; Bukhari, Syed Nasir Abbas

    2015-09-21

    The purpose of this study is to separate and identify the crystallin protein present in the nucleus of a human cataractous eye lens. Cataractous lenses were collected from different eye hospitals from patients of different etiologies with ages between 40 and 80 years. Lens nucleus proteins were extracted into four fractions on the basis of their solubility in different media by applying a reported method. These fractions were buffer-soluble proteins (PS), urea-soluble proteins (PU), yellow fraction proteins (PY) and insoluble proteins (PI). All three soluble fractions were subjected to HPLC and GPC analysis. Both HPLC and GPC analysis showed that each fraction contains α-, β- and γ-crystallins, a major class of protein present in the lenses of vertebrates. Various chromatographic parameters including precision, accuracy and linearity have been evaluated. Studies of water-insoluble crystallins using sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE) have demonstrated extreme homogeneity with evidence of major components with molecular masses of 18-70 kDa, similar to the crystallin of the water-soluble portion. The method was found to be suitable for the analysis of various isomers of crystallin protein present in human cataractous eye lens nuclei. The detailed results of the GPC are discussed. This study provides the first HPLC and GPC analysis of a human cataractous eye lens nucleus.

  17. 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

  18. Polarized Light for Measuring a Human Skin Feature Indicating Aging

    NASA Astrophysics Data System (ADS)

    Son, Jung-Young; Vashpanov, Yuriy A.; Jung, Dae-Hyun; Lee, Dong-Su; Kwack, Kae-Dal; Kim, Shin-Hwan

    2009-09-01

    The textures of skin on the back of the hand of many men of different ages are analyzed to determine their changes with age. The analysis shows that the textures are segmented by many lines of different lengths and orientations, and the size and number of segments in the skin surface change with age; that is the size increases while the number decreases. As a result, the texture becomes less complex with age. However, the addition of wrinkles from the age of 50 onwards for certain groups of people makes the texture appear somewhat complex.

  19. 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

    2015-01-01

    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

  20. 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

  1. Age-related accumulation of Ig VH gene somatic mutations in peripheral B cells from aged humans

    PubMed Central

    CHONG, Y; IKEMATSU, H; YAMAJI, K; NISHIMURA, M; KASHIWAGI, S; HAYASHI, J

    2003-01-01

    To investigate age-related alterations in human humoral immunity, we analysed Ig heavy chain variable region genes expressed by peripheral B cells from young and aged individuals. Three hundred and twenty-seven cDNA sequences, 163 µ and 164 γ transcripts with VH5 family genes, were analysed for somatic hypermutation and VHDJH recombinational features. Unmutated and mutated µ transcripts were interpreted as being from naive and memory IgM B cells, respectively. In young and aged individuals, the percentages of naive IgM among total µ transcripts were 39% and 42%, respectively. D and JH segment usage in naive IgM from aged individuals was similar to that from young individuals. The mutational frequencies of memory IgM were similar in young and aged individuals. γ transcripts, which are regarded as being from memory IgG B cells, showed a significantly higher mutational frequency (7·6%) in aged than in young individuals (5·8%) (P < 0·01). These findings suggest that VHDJH recombinational diversity was preserved, but that the accumulation of somatic mutations in the IgG VH region was increased in aged humans. The accumulation of somatic mutations in IgG B cells during ageing may imply that an age-related alteration exists in the selection and/or maintenance of peripheral memory B cells. PMID:12823279

  2. Quantification of lens opacification with a commercially available lensometer.

    PubMed Central

    Tuft, S J; Fitzke, F W; Lawrenson, J; Silver, J; Marshall, J

    1990-01-01

    A clinical trial was undertaken to determine whether a commercially available lens opacity meter (LM701), which measures backward scattered light from the lens, provides reliable clinical information about the effect of lens opacities on visual acuity. At the 0.001 level of probability we found a significant relationship between the lens opacity meter reading and both the Snellen acuity and patient's age. For a given individual there was also a relationship between the difference in the lens opacity readings between eyes and the difference in the Snellen acuities. We could not demonstrate a relation between the lens opacity reading and either the refractive error, pupil size, or near visual acuity at this level of significance. PMID:2178680

  3. Effects of transforming growth factor β2 and connective tissue growth factor on induction of epithelial mesenchymal transition and extracellular matrix synthesis in human lens epithelial cells

    PubMed Central

    Pei, Cheng; Ma, Bo; Kang, Qian-Yan; Qin, Li; Cui, Li-Jun

    2013-01-01

    AIM To investigate the effects of transforming growth factor β2 (TGF-β2) and connective tissue growth factor (CTGF) on transdifferentiation of human lens epithelial cells (HLECs) cultured in vitro and synthesis of extracellular matrix (ECM). METHODS HLECs were treated with TGF-β2 (0, 0.5, 1.0, 5, 10µg/L) and CTGF (0, 15, 30, 60, 100µg/L) for different times (0, 24, 48, 72h) in vitro and the expression of α-smooth muscle actin (α-SMA), the main component of the extracellular matrix type I collagen (Col-1) and fibronectin (Fn) were measured by using real-time polymerase chain reaction (PCR) and western-blot. RESULTS TGF-β2 and CTGF significantly increased expression of α-SMA mRNA and protein (P<0.05, P<0.001), Fn mRNA and protein (P<0.001), Col-1 mRNA and protein (P<0.001). TGF-β2 could induce HLECs expression of CTGF mRNA and protein in dose-dependent manner (P<0.05, P<0.001). TGF-β2 and CTGF could induce HLECs to express α-SMA, Fn and Col-1 in time-dependent manner. Each time of TGF-β2 and CTGF induced HELCs expression of α-SMA, Fn, Col-1 mRNA and protein was significant increase compared with control (P<0.05, P<0.001). CONCLUSION TGF-β2 and CTGF could induce HLECs epithelial mesenchymal transition and ECM synthesis. PMID:24392320

  4. 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.

  5. 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

  6. 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.

  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. Ultraviolet spectrograph lens

    SciTech Connect

    Brixner, B.; Winkler, M.A.

    1981-01-01

    A 700-mm f/4.7 spectrograph camera lens was designed for imaging spectral lines in the 200 to 400-nm region on a 120-mm flat image field. Lens elements of fused silica and crystalline calcium fluoride have so little secondary spectrum that raytracing calculations predict a monochromatic resolution limit of 30 lines/mm without refocusing in the 238- to 365-nm region. Light scattering at the polished calcium-fluoride surfaces is avoided by sandwiching the fluoride elements between fused silica and cementing with silicone fluid. The constructed lens makes good spectrograms.

  10. Ultraviolet-spectrograph lens

    SciTech Connect

    Brixner, B.; Winkler, M.A.

    1981-01-01

    A 700-mm f/4.7 spectrograph camera lens was designed for imaging spectral lines in the 200- to 400-nm region on a 120-mm flat image field. Lens elements of fused silica and crystal calcium fluoride give such good achromatization that raytracing calculations predict a resolution limit of 30 lines/mm without refocusing in the 238- to 365-nm region. Light scattering at the polished calcium-fluoride surfaces is avoided by sandwiching the fluoride elements between fused silica and cementing with silicone fluid. The constructed lens makes good spectrograms.

  11. 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.

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

    PubMed

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

    2015-06-01

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

  14. Forensic odontology: age determination from adult human teeth.

    PubMed

    Lampe, H; Roetzscher, K

    1994-01-01

    Dentistry has several recognized specialities. Age, race and sex determination together with dental identification and facial reconstruction on skeletal material are procedures that the forensic odontologist has to master. The use of Gustafson's method to determine age in an examination of 350 teeth of living and/or dead males and females from the Heidelberg area, Germany is discussed. PMID:7772197

  15. Hsp60 and human aging: Les liaisons dangereuses.

    PubMed

    Cappello, Francesco; Conway de Macario, Everly; Marino Gammazza, Antonella; Bonaventura, Giuseppe; Carini, Francesco; Czarnecka, Anna M; Farina, Felicia; Zummo, Giovanni; Macario, Alberto J L

    2013-01-01

    Stressors can cause abnormal intracellular accumulation of Hsp60 and its localization in extramitochondrial sites, secretion, and circulation, with immune system activation. Dysfunction of chaperones associated with their quantitative and qualitative decline with aging (chaperonopathies of aging) characterizes senescence and is a potential causal factor in the physiological deterioration that occurs with it. The role of Hsp60 in aging is not easy to elucidate, because aging is accompanied by pathologies (e.g., cardiovascular and neurodegenerative disorders, osteoporosis, diabetes, cancer, etc.) in which Hsp60 has been implicated but, although those disorders are more frequent in the elderly, they are not unique to them. Therefore, it is difficult to determine what is due to aging and what to an associated disease that can occur regardless of age. Does Hsp60 contribute to the pathogenesis? How and when does Hsp60 interact with the immune system and, thus, contributes to the initiation-progression of the generalized chronic inflammation characteristic of aging? These and related issues are discussed here in the light of reports showing the participation of Hsp60 in aging-associated disorders.

  16. Characterization of Skin Aging-Associated Secreted Proteins (SAASP) Produced by Dermal Fibroblasts Isolated from Intrinsically Aged Human Skin.

    PubMed

    Waldera Lupa, Daniel M; Kalfalah, Faiza; Safferling, Kai; Boukamp, Petra; Poschmann, Gereon; Volpi, Elena; Götz-Rösch, Christine; Bernerd, Francoise; Haag, Laura; Huebenthal, Ulrike; Fritsche, Ellen; Boege, Fritz; Grabe, Niels; Tigges, Julia; Stühler, Kai; Krutmann, Jean

    2015-08-01

    Most molecular hallmarks of cellular senescence have been identified in studies of cells aged in vitro by driving them into replicative or stress-induced senescence. Comparatively, less is known about the characteristic features of cells that have aged in vivo. Here we provide a systematic molecular analysis of normal human dermal fibroblasts (NHDFs) that were isolated from intrinsically aged human skin of young versus middle aged versus old donors. Intrinsically aged NHDFs in culture exhibited more frequently nuclear foci positive for p53 binding protein 1 and promyelocytic leukemia protein reminiscent of 'DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS)'. Formation of such foci was neither accompanied by increased DNA double strand breaks, nor decreased cell viability, nor telomere shortening. However, it was associated with the development of a secretory phenotype, indicating incipient cell senescence. By quantitative analysis of the entire secretome present in conditioned cell culture supernatant, combined with a multiplex cytokine determination, we identified 998 proteins secreted by intrinsically aged NHDFs in culture. Seventy of these proteins exhibited an age-dependent secretion pattern and were accordingly denoted 'skin aging-associated secreted proteins (SAASP)'. Systematic comparison of SAASP with the classical senescence-associated secretory phenotype (SASP) revealed that matrix degradation as well as proinflammatory processes are common aspects of both conditions. However, secretion of 27 proteins involved in the biological processes of 'metabolism' and 'adherens junction interactions' was unique for NHDFs isolated from intrinsically aged skin. In conclusion, fibroblasts isolated from intrinsically aged skin exhibit some, but not all, molecular hallmarks of cellular senescence. Most importantly, they secrete a unique pattern of proteins that is distinct from the canonical SASP and might reflect specific processes of skin aging

  17. Characterization of Skin Aging-Associated Secreted Proteins (SAASP) Produced by Dermal Fibroblasts Isolated from Intrinsically Aged Human Skin.

    PubMed

    Waldera Lupa, Daniel M; Kalfalah, Faiza; Safferling, Kai; Boukamp, Petra; Poschmann, Gereon; Volpi, Elena; Götz-Rösch, Christine; Bernerd, Francoise; Haag, Laura; Huebenthal, Ulrike; Fritsche, Ellen; Boege, Fritz; Grabe, Niels; Tigges, Julia; Stühler, Kai; Krutmann, Jean

    2015-08-01

    Most molecular hallmarks of cellular senescence have been identified in studies of cells aged in vitro by driving them into replicative or stress-induced senescence. Comparatively, less is known about the characteristic features of cells that have aged in vivo. Here we provide a systematic molecular analysis of normal human dermal fibroblasts (NHDFs) that were isolated from intrinsically aged human skin of young versus middle aged versus old donors. Intrinsically aged NHDFs in culture exhibited more frequently nuclear foci positive for p53 binding protein 1 and promyelocytic leukemia protein reminiscent of 'DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS)'. Formation of such foci was neither accompanied by increased DNA double strand breaks, nor decreased cell viability, nor telomere shortening. However, it was associated with the development of a secretory phenotype, indicating incipient cell senescence. By quantitative analysis of the entire secretome present in conditioned cell culture supernatant, combined with a multiplex cytokine determination, we identified 998 proteins secreted by intrinsically aged NHDFs in culture. Seventy of these proteins exhibited an age-dependent secretion pattern and were accordingly denoted 'skin aging-associated secreted proteins (SAASP)'. Systematic comparison of SAASP with the classical senescence-associated secretory phenotype (SASP) revealed that matrix degradation as well as proinflammatory processes are common aspects of both conditions. However, secretion of 27 proteins involved in the biological processes of 'metabolism' and 'adherens junction interactions' was unique for NHDFs isolated from intrinsically aged skin. In conclusion, fibroblasts isolated from intrinsically aged skin exhibit some, but not all, molecular hallmarks of cellular senescence. Most importantly, they secrete a unique pattern of proteins that is distinct from the canonical SASP and might reflect specific processes of skin aging.

  18. 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 ...

  19. 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.

  20. 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.

  1. 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

  2. Human Age Estimation Based on Locality and Ordinal Information.

    PubMed

    Li, Changsheng; Liu, Qingshan; Dong, Weishan; Zhu, Xiaobin; Liu, Jing; Lu, Hanqing

    2015-11-01

    In this paper, we propose a novel feature selection-based method for facial age estimation. The face aging is a typical temporal process, and facial images should have certain ordinal patterns in the aging feature space. From the geometrical perspective, a facial image can be usually seen as sampled from a low-dimensional manifold embedded in the original high-dimensional feature space. Thus, we first measure the energy of each feature in preserving the underlying local structure information and the ordinal information of the facial images, respectively, and then we intend to learn a low-dimensional aging representation that can maximally preserve both kinds of information. To further improve the performance, we try to eliminate the redundant local information and ordinal information as much as possible by minimizing nonlinear correlation and rank correlation among features. Finally, we formulate all these issues into a unified optimization problem, which is similar to linear discriminant analysis in format. Since it is expensive to collect the labeled facial aging images in practice, we extend the proposed supervised method to a semi-supervised learning mode including the semi-supervised feature selection method and the semi-supervised age prediction algorithm. Extensive experiments are conducted on the FACES dataset, the Images of Groups dataset, and the FG-NET aging dataset to show the power of the proposed algorithms, compared to the state-of-the-arts. PMID:26470062

  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. Terahertz Artificial Dielectric Lens.

    PubMed

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

    2016-01-01

    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. PMID:26973294

  5. Terahertz Artificial Dielectric Lens.

    PubMed

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

    2016-03-14

    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.

  6. Terahertz Artificial Dielectric Lens

    PubMed Central

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

    2016-01-01

    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. PMID:26973294

  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. PMID:26608482

  8. Molecular consequences of psychological stress in human aging.

    PubMed

    Moreno-Villanueva, M; Bürkle, A

    2015-08-01

    Psychological stress has often been described as a feeling of being overwhelmed by the necessity of constant adjustment to an individual's changing environment. Stress affects people of all ages, but the lives of the elderly may particularly be affected. Major changes can cause anxiety leading to feelings of insecurity and/or loss of self-esteem and depression. The cellular mechanisms underlying psychological stress are poorly understood. This review focuses on the physical and molecular consequences of psychological stress linked to aging processes and, in particular, how molecular changes induced by psychological stress can compromise healthy aging.

  9. Molecular consequences of psychological stress in human aging.

    PubMed

    Moreno-Villanueva, M; Bürkle, A

    2015-08-01

    Psychological stress has often been described as a feeling of being overwhelmed by the necessity of constant adjustment to an individual's changing environment. Stress affects people of all ages, but the lives of the elderly may particularly be affected. Major changes can cause anxiety leading to feelings of insecurity and/or loss of self-esteem and depression. The cellular mechanisms underlying psychological stress are poorly understood. This review focuses on the physical and molecular consequences of psychological stress linked to aging processes and, in particular, how molecular changes induced by psychological stress can compromise healthy aging. PMID:25481270

  10. Human dental age estimation combining third molar(s) development and tooth morphological age predictors.

    PubMed

    Thevissen, P W; Galiti, D; Willems, G

    2012-11-01

    In the subadult age group, third molar development, as well as age-related morphological tooth information can be observed on panoramic radiographs. The aim of present study was to combine, in subadults, panoramic radiographic data based on developmental stages of third molar(s) and morphological measurements from permanent teeth, in order to evaluate its added age-predicting performances. In the age range between 15 and 23 years, 25 gender-specific radiographs were collected within each age category of 1 year. Third molar development was classified and registered according the 10-point staging and scoring technique proposed by Gleiser and Hunt (1955), modified by Köhler (1994). The Kvaal (1995) measuring technique was applied on the indicated teeth from the individuals' left side. Linear regression models with age as response and third molar-scored stages as explanatory variables were developed, and morphological measurements from permanent teeth were added. From the models, determination coefficients (R (2)) and root-mean-square errors (RMSE) were calculated. Maximal-added age information was reported as a 6 % R² increase and a 0.10-year decrease of RMSE. Forensic dental age estimations on panoramic radiographic data in the subadult group (15-23 year) should only be based on third molar development.

  11. Health Through the Urban Lens

    PubMed Central

    2008-01-01

    Cities are now the major sites of human habitation worldwide, a trend that will continue for the foreseeable future, not only in the developed world but in developing countries. Urban residence impacts health and health prospects both positively and negatively through a complex mix of exposures and mechanisms. In addition, cities concentrate population subsets of various demographic, economic, and social characteristics, some with particular health risks and vulnerabilities. Looking at health through the urban lens allows increased understanding of disparate risks and emphasizes the essentiality of collaborative efforts in protecting and enhancing the health of populations, especially those living in cities. PMID:18668367

  12. Oxidative Stress, Aging and CNS disease in the Canine Model of Human Brain Aging

    PubMed Central

    Head, Elizabeth; Rofina, Jaime; Zicker, Steven

    2008-01-01

    SYNOPSIS Decline in cognitive functions that accompany aging in dogs may have a biological basis, and many of the disorders associated with aging in canines may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of both laboratory and clinical studies – antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs. However, determining all effective compounds and combinations, dosage ranges, as well as when to initiate intervention and long term effects constitute gaps in our current knowledge. PMID:18249248

  13. Oxidative stress, aging, and central nervous system disease in the canine model of human brain aging.

    PubMed

    Head, Elizabeth; Rofina, Jaime; Zicker, Steven

    2008-01-01

    Decline in cognitive functions that accompany aging in dogs may have a biologic basis, and many of the disorders associated with aging in dogs may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs.

  14. Increased age of transformed mouse neural progenitor/stem cells recapitulates age-dependent clinical features of human glioma malignancy

    PubMed Central

    Mikheev, Andrei M.; Ramakrishna, Rohan; Stoll, Elizabeth A.; Mikheeva, Svetlana A.; Beyer, Richard P.; Plotnik, David A.; Schwartz, Jeffrey L.; Rockhill, Jason K.; Silber, John R.; Born, Donald E.; Kosai, Yoshito; Horner, Philip J.; Rostomily, Robert C.

    2012-01-01

    Increasing age is the most robust predictor of greater malignancy and treatment resistance in human gliomas. However, the adverse association of clinical course with aging is rarely considered in animal glioma models, impeding delineation of the relative importance of organismal versus progenitor cell aging in the genesis of glioma malignancy. To address this limitation, we implanted transformed neural stem/progenitor cells (NSPCs), the presumed cells of glioma origin, from 3 and 18month old mice into 3 and 20-month host animals. Transplantation with progenitors from older animals resulted in significantly shorter (p ≤ 0.0001) median survival in both 3month (37.5 vs 83 days) and 20-month (38 vs 67 days) hosts, indicating that age-dependent changes intrinsic to NSPCs rather than host animal age accounted for greater malignancy. Subsequent analyses revealed that increased invasiveness, genomic instability, resistance to therapeutic agents and tolerance to hypoxic stress accompanied aging in transformed NSPCs. Greater tolerance to hypoxia in older progenitor cells, as evidenced by elevated HIF-1 promoter reporter activity and hypoxia response gene (HRG) expression, mirror the upregulation of HRGs in cohorts of older vs younger glioma patients revealed by analysis of gene expression databases, suggesting that differential response to hypoxic stress may underlie age-dependent differences in invasion, genomic instability and treatment resistance. Our study provides strong evidence that progenitor cell aging is responsible for promoting the hallmarks of age-dependent glioma malignancy and that consideration of progenitor aging will facilitate development of physiologically and clinically relevant animal models of human gliomas. PMID:22958206

  15. 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.

  16. 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…

  17. 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...

  18. Chronologic and actinically induced aging in human facial skin

    SciTech Connect

    Gilchrest, B.A.; Szabo, G.; Flynn, E.; Goldwyn, R.M.

    1983-06-01

    Clinical and histologic stigmata of aging are much more prominent in habitually sun-exposed skin than in sun-protected skin, but other possible manifestations of actinically induced aging are almost unexplored. We have examined the interrelation of chronologic and actinic aging using paired preauricular (sun-exposed) and postauricular (sun-protected) skin specimens. Keratinocyte cultures derived from sun-exposed skin consistently had a shorter in vitro lifespan but increased plating efficiency compared with cultures derived from adjacent sun-protected skin of the same individual, confirming a previous study of different paired body sites. Electron microscopic histologic sections revealed focal abnormalities of keratinocyte proliferation and alignment in vitro especially in those cultures derived from sun-exposed skin and decreased intercellular contact in stratified colonies at late passage, regardless of donor site. One-micron histologic sections of the original biopsy specimens revealed no striking site-related keratinocyte alterations, but sun-exposed specimens had fewer epidermal Langerhans cells (p less than 0.001), averaging approximately 50 percent the number in sun-protected skin, a possible exaggeration of the previously reported age-associated decrease in this cell population. These data suggest that sun exposure indeed accelerates aging by several criteria and that, regardless of mechanism, environmental factors may adversely affect the appearance and function of aging skin in ways amenable to experimental quantitation.

  19. Behavior analysis and the study of human aging

    PubMed Central

    Derenne, Adam; Baron, Alan

    2002-01-01

    As the population of older adults continues to rise, psychologists along with other behavioral and social scientists have shown increasing interest in this age group. Although behavior analysts have contributed to research on aging, the focus has been on applications that remedy age-related deficits, rather than a concern with aging as a developmental process. In particular, there has been little interest in the central theoretical questions that have guided gerontologists. How does behavior change with advancing years, and what are the sources of those changes? We consider the possibility that this neglect reflects the long-standing commitment of behavior analysts to variables that can be experimentally manipulated, a requirement that excludes the key variable—age itself. We review the options available to researchers and present strategies that minimize deviations from the traditional features of behavior-analytic designs. Our comments are predicated on the view that aging issues within contemporary society are far too important for behavior analysts to ignore. PMID:22478383

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

    PubMed

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

    2011-01-01

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

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

    PubMed

    Ruetenik, Andrea; Barrientos, Antoni

    2015-11-01

    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 health-span and lifespan. This article is part of a Special Issue entitled: Mitochondrial Dysfunction in Aging.

  2. Hedgehog signaling maintains hair follicle stem cell phenotype in young and aged human skin.

    PubMed

    Rittié, Laure; Stoll, Stefan W; Kang, Sewon; Voorhees, John J; Fisher, Gary J

    2009-12-01

    Skin hair follicles (HF) contain bulge stem cells (SC) that regenerate HFs during hair cycles, and repair skin epithelia following injury. As natural aging is associated with decreased skin repair capacity in humans, we have investigated the impact of age on human scalp HF bulge cell number and function. Here, we isolated human bulge cells, characterized as CD200+/KRT15+/KRT19+ cells of the HF, by dissection-combined CD200 selection in young and aged human skin. Targeted transcriptional profiling indicates that KRT15, KRT19, Dkk3, Dkk4, Tcf3, S100A4, Gas1, EGFR and CTGF/CCN2 are also preferentially expressed by human bulge cells, compared to differentiated HF keratinocytes (KC). Our results demonstrate that aging does not alter expression or localization of these HF SC markers. In addition, we could not detect significant differences in HF density or bulge cell number between young and aged human scalp skin. Interestingly, hedgehog (Hh) signaling is activated in human bulge cells in vivo, and down-regulated in differentiated HF KCs, both in young and aged skin. In addition, activation of Hh signaling by lentivirus-mediated overexpression of transcription factor Gli1 induces transcription of HF SC markers KRT15, KRT19, and Gas1, in cultured KCs. Together with previously reported knock-out mouse results, these data suggest a role for Hh signaling in maintaining bulge cell phenotype in young and aged human skin.

  3. Genome Integrity in Aging: Human Syndromes, Mouse Models, and Therapeutic Options.

    PubMed

    Vermeij, Wilbert P; Hoeijmakers, Jan H J; Pothof, Joris

    2016-01-01

    Human syndromes and mouse mutants that exhibit accelerated but bona fide aging in multiple organs and tissues have been invaluable for the identification of nine denominators of aging: telomere attrition, genome instability, epigenetic alterations, mitochondrial dysfunction, deregulated nutrient sensing, altered intercellular communication, loss of proteostasis, cellular senescence and adult stem cell exhaustion. However, whether and how these instigators of aging interrelate or whether they have one root cause is currently largely unknown. Rare human progeroid syndromes and corresponding mouse mutants with resolved genetic defects highlight the dominant importance of genome maintenance for aging. A second class of aging-related disorders reveals a cross connection with metabolism. As genome maintenance and metabolism are closely interconnected, they may constitute the main underlying biology of aging. This review focuses on the role of genome stability in aging, its crosstalk with metabolism, and options for nutritional and/or pharmaceutical interventions that delay age-related pathology.

  4. Genome Integrity in Aging: Human Syndromes, Mouse Models, and Therapeutic Options.

    PubMed

    Vermeij, Wilbert P; Hoeijmakers, Jan H J; Pothof, Joris

    2016-01-01

    Human syndromes and mouse mutants that exhibit accelerated but bona fide aging in multiple organs and tissues have been invaluable for the identification of nine denominators of aging: telomere attrition, genome instability, epigenetic alterations, mitochondrial dysfunction, deregulated nutrient sensing, altered intercellular communication, loss of proteostasis, cellular senescence and adult stem cell exhaustion. However, whether and how these instigators of aging interrelate or whether they have one root cause is currently largely unknown. Rare human progeroid syndromes and corresponding mouse mutants with resolved genetic defects highlight the dominant importance of genome maintenance for aging. A second class of aging-related disorders reveals a cross connection with metabolism. As genome maintenance and metabolism are closely interconnected, they may constitute the main underlying biology of aging. This review focuses on the role of genome stability in aging, its crosstalk with metabolism, and options for nutritional and/or pharmaceutical interventions that delay age-related pathology. PMID:26514200

  5. 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.

  6. 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.

  7. 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

  8. Age-Related Cognitive Deficits In Rhesus Monkeys Mirror Human Deficits on an Automated Test Battery

    PubMed Central

    Nagahara, Alan H.; Bernot, Tim; Tuszynski, Mark H.

    2010-01-01

    Aged non-human primates are a valuable model for gaining insight into mechanisms underlying neural decline with aging and during the course of neurodegenerative disorders. Behavioral studies are a valuable component of aged primate models, but are difficult to perform, time consuming, and often of uncertain relevance to human cognitive measures. We now report findings from an automated cognitive test battery in aged primates using equipment that is identical, and tasks that are similar, to those employed in human aging and Alzheimer’s disease studies. Young (7.1 ± 0.8 years) and aged (23.0 ± 0.5 years) rhesus monkeys underwent testing on a modified version of the Cambridge Automated Neuropsychological Test Battery (CANTAB), examining cognitive performance on separate tasks that sample features of visuospatial learning, spatial working memory, discrimination learning, and skilled motor performance. We find selective cognitive impairments among aged subjects in visuospatial learning and spatial working memory, but not in delayed recall of previously learned discriminations. Aged monkeys also exhibit slower speed in skilled motor function. Thus, aged monkeys behaviorally characterized on a battery of automated tests reveal patterns of age-related cognitive impairment that mirror in quality and severity those of aged humans, and differ fundamentally from more severe patterns of deficits observed in Alzheimer’s Disease. PMID:18760505

  9. 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. PMID:19838277

  10. Geometry-invariant gradient refractive index lens: analytical ray tracing

    NASA Astrophysics Data System (ADS)

    Bahrami, Mehdi; Goncharov, Alexander V.

    2012-05-01

    A new class of gradient refractive index (GRIN) lens is introduced and analyzed. The interior iso-indicial contours mimic the external shape of the lens, which leads to an invariant geometry of the GRIN structure. The lens model employs a conventional surface representation using a coincoid of revolution with a higher-order aspheric term. This model has a unique feature, namely, it allows analytical paraxial ray tracing. The height and the angle of an arbitrary incident ray can be found inside the lens in a closed-form expression, which is used to calculate the main optical characteristics of the lens, including the optical power and third-order monochromatic aberration coefficients. Moreover, due to strong coupling of the external surface shape to the GRIN structure, the proposed GRIN lens is well suited for studying accommodation mechanism in the eye. To show the power of the model, several examples are given emphasizing the usefulness of the analytical solution. The presented geometry-invariant GRIN lens can be used for modeling and reconstructing the crystalline lens of the human eye and other types of eyes featuring a GRIN lens.

  11. Age-related decline in ovarian follicle stocks differ between chimpanzees (Pan troglodytes) and humans.

    PubMed

    Cloutier, Christina T; Coxworth, James E; Hawkes, Kristen

    2015-02-01

    Similarity in oldest parturitions in humans and great apes suggests that we maintain ancestral rates of ovarian aging. Consistent with that hypothesis, previous counts of primordial follicles in postmortem ovarian sections from chimpanzees (Pan troglodytes) showed follicle stock decline at the same rate that human stocks decline across the same ages. Here, we correct that finding with a chimpanzee sample more than three times larger than the previous one, which also allows comparison into older ages. Analyses show depletion rates similar until about age 35, but after 35, the human counts continue to fall with age, while the change is much less steep in chimpanzees. This difference implicates likely effects on ovarian dynamics from other physiological systems that are senescing at different rates, and, potentially, different perimenopausal experience for chimpanzees and humans.

  12. 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.

  13. Paternal Age and Numerical Chromosome Abnormalities in Human Spermatozoa.

    PubMed

    Donate, Anna; Estop, Anna M; Giraldo, Jesús; Templado, Cristina

    2016-01-01

    This study explores the relationship between numerical chromosome abnormalities in sperm and age in healthy men. We performed FISH in the spermatozoa of 10 donors from the general population: 5 men younger than 40 years of age and 5 fertile men older than 60 years of age. For each chromosome, 1,000 sperm nuclei were analyzed, with a total of 15,000 sperm nuclei for each donor. We used a single sperm sample per donor, thus minimizing intra-donor variability and optimizing consistent analysis. FISH with a TelVysion assay, which provides data on aneuploidy of 19 chromosomes, was used in order to gain a more genome-wide perspective of the level of aneuploidy. Aneuploidy and diploidy rates observed in the younger and older groups were compared. There were no significant differences in the incidence of autosomal disomy, sex chromosome disomy, total chromosome disomy, diploidy, nor total numerical abnormalities between younger and older men. This work confirms that aneuploidy of the sex chromosomes is more common than that of autosomes and that this does not change with age. Our results suggest that some probe combinations have a tendency to indicate higher levels of diploidy, thus potentially affecting FISH results and highlighting the limitations of FISH. PMID:27322585

  14. Tunable optofluidic birefringent lens.

    PubMed

    Wee, D; Hwang, S H; Song, Y S; Youn, J R

    2016-05-01

    An optofluidic birefringent lens is demonstrated using hydrodynamic liquid-liquid (L(2)) interfaces in a microchannel. The L(2) lens comprises a nematic liquid crystal (NLC) phase and an optically isotropic phase for the main stream and the surrounding sub-stream, respectively. When the optofluidic device is subjected to a sufficiently strong electric field perpendicular to the flow direction, NLCs are allowed to orient along the external field rather than the flow direction overcoming fluidic viscous stress. The characteristics of the optofluidic birefringence lens are investigated by experimental and numerical analyses. The difference between the refractive indices of the main stream and the sub-stream changes according to the polarization direction of incident light, which determines the optical behaviour of the lens. The incidence of s-polarized light leads to a short focal point, while p-polarized light has a relatively long focal distance from the same L(2) interface. The curvatures and focal lengths of the lens are successfully evaluated by a hydrodynamic theory of NLCs and a simple ray-tracing model. PMID:27035877

  15. Human age estimation combining third molar and skeletal development.

    PubMed

    Thevissen, P W; Kaur, J; Willems, G

    2012-03-01

    The wide prediction intervals obtained with age estimation methods based on third molar development could be reduced by combining these dental observations with age-related skeletal information. Therefore, on cephalometric radiographs, the most accurate age-estimating skeletal variable and related registration method were searched and added to a regression model, with age as response and third molar stages as explanatory variable. In a pilot set up on a dataset of 496 (283 M; 213 F) cephalometric radiographs, the techniques of Baccetti et al. (2005) (BA), Seedat et al. (2005) (SE), Caldas et al. (2007) and Rai et al. (2008) (RA) were verified. In the main study, data from 460 (208 F, 224 M) individuals in an age range between 3 and 26 years, for which at the same day an orthopantogram and a cephalogram were taken, were collected. On the orthopantomograms, the left third molar development was registered using the scoring system described by Gleiser and Hunt (1955) and modified by Köhler (1994) (GH). On the cephalograms, cervical vertebrae development was registered according to the BA and SE techniques. A regression model, with age as response and the GH scores as explanatory variable, was fitted to the data. Next, information of BA, SE and BA + SE was, respectively, added to this model. From all obtained models, the determination coefficients and the root mean squared errors were calculated. Inclusion of information from cephalograms based on the BA, as well as the SE, technique improved the amount of explained variance in age acquired from panoramic radiographs using the GH technique with 48%. Inclusion of cephalometric BA + SE information marginally improved the previous result (+1%). The RMSE decreased with 1.93, 1.85 and 2.03 years by adding, respectively, BA, SE and BA + SE information to the GH model. The SE technique allows clinically the fastest and easiest registration of the degree of development of the cervical vertebrae. Therefore, the choice of

  16. Cardiac Aging in Mice and Humans: the Role of Mitochondrial Oxidative Stress

    PubMed Central

    Dai, Dao-Fu; Rabinovitch, Peter S.

    2009-01-01

    Age is a major risk factor for cardiovascular diseases, not only because it prolongs exposure to several other cardiovascular risks, but also owing to intrinsic cardiac aging, which reduces cardiac functional reserve, predisposes the heart to stress and contributes to increased cardiovascular mortality in the elderly. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans, including left ventricular hypertrophy, fibrosis and diastolic dysfunction. Cardiac aging in mice is accompanied by accumulation of mitochondrial protein oxidation, increased mitochondrial DNA mutations, increased mitochondrial biogenesis, as well as decreased cardiac SERCA2 protein. All of these age-related changes are significantly attenuated in mice overexpressing catalase targeted to mitochondria (mCAT). These findings demonstrate the critical role of mitochondrial reactive oxygen species (ROS) in cardiac aging and support the potential application of mitochondrial antioxidants to cardiac aging and age-related cardiovascular diseases. PMID:20382344

  17. Effect of aging on muscle mitochondrial substrate utilization in humans

    PubMed Central

    Petersen, Kitt Falk; Morino, Katsutaro; Alves, Tiago C.; Kibbey, Richard G.; Dufour, Sylvie; Sono, Saki; Yoo, Peter S.; Cline, Gary W.; Shulman, Gerald I.

    2015-01-01

    Previous studies have implicated age-associated reductions in mitochondrial oxidative phosphorylation activity in skeletal muscle as a predisposing factor for intramyocellular lipid (IMCL) accumulation and muscle insulin resistance (IR) in the elderly. To further investigate potential alterations in muscle mitochondrial function associated with aging, we assessed basal and insulin-stimulated rates of muscle pyruvate dehydrogenase (VPDH) flux relative to citrate synthase flux (VCS) in healthy lean, elderly subjects and healthy young body mass index- and activity-matched subjects. VPDH/VCS flux was assessed from the 13C incorporation from of infused [1-13C] glucose into glutamate [4-13C] relative to alanine [3-13C] assessed by LC-tandem MS in muscle biopsies. Insulin-stimulated rates of muscle glucose uptake were reduced by 25% (P < 0.01) in the elderly subjects and were associated with ∼70% (P < 0.04) increase in IMCL, assessed by 1H magnetic resonance spectroscopy. Basal VPDH/VCS fluxes were similar between the groups (young: 0.20 ± 0.03; elderly: 0.14 ± 0.03) and increased approximately threefold in the young subjects following insulin stimulation. However, this increase was severely blunted in the elderly subjects (young: 0.55 ± 0.04; elderly: 0.18 ± 0.02, P = 0.0002) and was associated with an ∼40% (P = 0.004) reduction in insulin activation of Akt. These results provide new insights into acquired mitochondrial abnormalities associated with aging and demonstrate that age-associated reductions in muscle mitochondrial function and increased IMCL are associated with a marked inability of mitochondria to switch from lipid to glucose oxidation during insulin stimulation. PMID:26305973

  18. Interacting Socially with Human Hands at 24 Months of Age

    ERIC Educational Resources Information Center

    Slaughter, Virginia; Nielsen, Mark; Enchelmaier, Petrina

    2008-01-01

    This experiment explored whether or not 2-year-olds would engage in synchronic imitation with human hands. Sixty-four 24-month-old infants participated. In a test of synchronic imitation, infants were given a toy while a model simultaneously performed novel actions on an identical toy. Infants were randomly assigned to 1 of 4 model conditions: a…

  19. 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.

  20. Metamaterial lens design

    NASA Astrophysics Data System (ADS)

    Shepard, Ralph Hamilton, III

    Developments in nanotechnology and material science have produced optical materials with astonishing properties. Theory and experimentation have demonstrated that, among other properties, the law of refraction is reversed at an interface between a naturally occurring material and these so-called metamaterials. As the technology advances metamaterials have the potential to vastly impact the field of optical science. In this study we provide a foundation for future work in the area of geometric optics and lens design with metamaterials. The concept of negative refraction is extended to derive a comprehensive set of first-order imaging principles as well as an exhaustive aberration theory to 4th order. Results demonstrate congruence with the classical theory; however, negative refraction introduces a host of novel properties. In terms of aberration theory, metamaterials present the lens designer with increased flexibility. A singlet can be bent to produce either positive or negative spherical aberration (regardless of its focal length), its contribution to coma can become independent of its conjugate factor, and its field curvature takes on the opposite sign of its focal power. This is shown to be advantageous in some designs such as a finite conjugate relay lens; however, in a wider field of view landscape lens we demonstrate a metamaterial's aberration properties may be detrimental. This study presents the first comprehensive investigation of metamaterial lenses using industry standard lens design software. A formal design study evaluates the performance of doublet and triplet lenses operating at F/5 with a 100 mm focal length, a 20° half field of view, and specific geometric constraints. Computer aided optimization and performance evaluation provide experimental controls to remove designer-induced bias from the results. Positive-index lenses provide benchmarks for comparison to metamaterial systems subjected to identical design constraints. We find that

  1. 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.

  2. 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.

  3. Effects of Aging on Genioglossus Motor Units in Humans

    PubMed Central

    Saboisky, Julian P.; Stashuk, Daniel W.; Hamilton-Wright, Andrew; Trinder, John; Nandedkar, Sanjeev; Malhotra, Atul

    2014-01-01

    The genioglossus is a major upper airway dilator muscle thought to be important in obstructive sleep apnea pathogenesis. Aging is a risk factor for obstructive sleep apnea although the mechanisms are unclear and the effects of aging on motor unit remodeled in the genioglossus remains unknown. To assess possible changes associated with aging we compared quantitative parameters related to motor unit potential morphology derived from EMG signals in a sample of older (n = 11; >55 years) versus younger (n = 29; <55 years) adults. All data were recorded during quiet breathing with the subjects awake. Diagnostic sleep studies (Apnea Hypopnea Index) confirmed the presence or absence of obstructive sleep apnea. Genioglossus EMG signals were analyzed offline by automated software (DQEMG), which estimated a MUP template from each extracted motor unit potential train (MUPT) for both the selective concentric needle and concentric needle macro (CNMACRO) recorded EMG signals. 2074 MUPTs from 40 subjects (mean±95% CI; older AHI 19.6±9.9 events/hr versus younger AHI 30.1±6.1 events/hr) were extracted. MUPs detected in older adults were 32% longer in duration (14.7±0.5 ms versus 11.1±0.2 ms; P  =  0.05), with similar amplitudes (395.2±25.1 µV versus 394.6±13.7 µV). Amplitudes of CNMACRO MUPs detected in older adults were larger by 22% (62.7±6.5 µV versus 51.3±3.0 µV; P<0.05), with areas 24% larger (160.6±18.6 µV.ms versus 130.0±7.4 µV.ms; P<0.05) than those detected in younger adults. These results confirm that remodeled motor units are present in the genioglossus muscle of individuals above 55 years, which may have implications for OSA pathogenesis and aging related upper airway collapsibility. PMID:25111799

  4. 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.

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

    PubMed

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

    2015-10-01

    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.

  6. Effects of Aging and Anatomic Location on Gene Expression in Human Retina

    PubMed Central

    Cai, Hui; Fields, Mark A.; Hoshino, Risa; Priore, Lucian V. Del

    2012-01-01

    Objective: To determine the effects of age and topographic location on gene expression in human neural retina. Methods: Macular and peripheral neural retina RNA was isolated from human donor eyes for DNA microarray and quantitative RT-PCR analyses. Results: Total RNA integrity from human donors was preserved. Hierarchical clustering analysis demonstrates that the gene expression profiles of young, old, macula, and peripheral retina cluster into four distinct groups. Genes which are highly expressed in macular, peripheral, young, or old retina were identified, including inhibitors of Wnt Signaling Pathway (DKK1, FZD10, and SFRP2) which are preferably expressed in the periphery. Conclusion: The transcriptome of the human retina is affected by age and topographic location. Wnt pathway inhibitors in the periphery may maintain peripheral retinal cells in an undifferentiated state. Understanding the effects of age and topographic location on gene expression may lead to the development of new therapeutic interventions for age-related eye diseases. PMID:22666212

  7. 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...

  8. Reduced DNA methylation patterning and transcriptional connectivity define human skin aging.

    PubMed

    Bormann, Felix; Rodríguez-Paredes, Manuel; Hagemann, Sabine; Manchanda, Himanshu; Kristof, Boris; Gutekunst, Julian; Raddatz, Günter; Haas, Rainer; Terstegen, Lara; Wenck, Horst; Kaderali, Lars; Winnefeld, Marc; Lyko, Frank

    2016-06-01

    Epigenetic changes represent an attractive mechanism for understanding the phenotypic changes associated with human aging. Age-related changes in DNA methylation at the genome scale have been termed 'epigenetic drift', but the defining features of this phenomenon remain to be established. Human epidermis represents an excellent model for understanding age-related epigenetic changes because of its substantial cell-type homogeneity and its well-known age-related phenotype. We have now generated and analyzed the currently largest set of human epidermis methylomes (N = 108) using array-based profiling of 450 000 methylation marks in various age groups. Data analysis confirmed that age-related methylation differences are locally restricted and characterized by relatively small effect sizes. Nevertheless, methylation data could be used to predict the chronological age of sample donors with high accuracy. We also identified discontinuous methylation changes as a novel feature of the aging methylome. Finally, our analysis uncovered an age-related erosion of DNA methylation patterns that is characterized by a reduced dynamic range and increased heterogeneity of global methylation patterns. These changes in methylation variability were accompanied by a reduced connectivity of transcriptional networks. Our findings thus define the loss of epigenetic regulatory fidelity as a key feature of the aging epigenome.

  9. The effect of ageing on human platelet sensitivity to serotonin.

    PubMed

    Gleerup, G; Winther, K

    1988-10-01

    Twelve healthy young volunteers (mean age 21, range 18-27 years) and 12 elderly people (mean age 77, range 72-86 years) were tested regarding platelet aggregation induced by adrenaline, ADP and serotonin. The serum levels of thromboxane B2 (TXB2) and serum 6-keto-PGF1 alpha and the plasma level of adrenaline and cyclic AMP (cAMP) were also measured. Platelet aggregation induced by adrenaline and ADP increased significantly in the elderly compared with the young group (P less than 0.05 and P less than 0.02, respectively). There was a substantial and highly significant increase in the response of platelets from elderly people to serotonin (P less than 0.01). No alteration was observed in the serum level of TXB2 or 6-keto-PGF1 alpha. Plasma adrenaline increased in the old group, but plasma cAMP was unaffected. As serotonin is known to amplify adrenaline- and ADR-induced platelet aggregation, the considerable increase in platelet sensitivity to serotonin could be an important factor in the increased adrenaline and ADP-induced platelet aggregability of elderly people.

  10. 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

  11. Age-Related Changes of Myelin Basic Protein in Mouse and Human Auditory Nerve

    PubMed Central

    Xing, Yazhi; Samuvel, Devadoss J.; Stevens, Shawn M.; Dubno, Judy R.; Schulte, Bradley A.; Lang, Hainan

    2012-01-01

    Age-related hearing loss (presbyacusis) is the most common type of hearing impairment. One of the most consistent pathological changes seen in presbyacusis is the loss of spiral ganglion neurons (SGNs). Defining the cellular and molecular basis of SGN degeneration in the human inner ear is critical to gaining a better understanding of the pathophysiology of presbyacusis. However, information on age-related cellular and molecular alterations in the human spiral ganglion remains scant, owing to the very limited availably of human specimens suitable for high resolution morphological and molecular analysis. This study aimed at defining age-related alterations in the auditory nerve in human temporal bones and determining if immunostaining for myelin basic protein (MBP) can be used as an alternative approach to electron microscopy for evaluating myelin degeneration. For comparative purposes, we evaluated ultrastructural alternations and changes in MBP immunostaining in aging CBA/CaJ mice. We then examined 13 temporal bones from 10 human donors, including 4 adults aged 38–46 years (middle-aged group) and 6 adults aged 63–91 years (older group). Similar to the mouse, intense immunostaining of MBP was present throughout the auditory nerve of the middle-aged human donors. Significant declines in MBP immunoreactivity and losses of MBP+ auditory nerve fibers were observed in the spiral ganglia of both the older human and aged mouse ears. This study demonstrates that immunostaining for MBP in combination with confocal microscopy provides a sensitive, reliable, and efficient method for assessing alterations of myelin sheaths in the auditory nerve. The results also suggest that myelin degeneration may play a critical role in the SGN loss and the subsequent decline of the auditory nerve function in presbyacusis. PMID:22496821

  12. 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…

  13. Lens proteome map and alpha-crystallin profile of the catfish Rita rita.

    PubMed

    Mohanty, Bimal Prasanna; Bhattacharjee, Soma; Das, Manas Kumar

    2011-02-01

    Crystallins are a diverse group of proteins that constitute nearly 90% of the total soluble proteins of the vertebrate eye lens and these tightly packed crystallins are responsible for transparency of the lens. These proteins have been studied in different model and non-model species for understanding the modifications they undergo with ageing that lead to cataract, a disease of protein aggregation. In the present investigation, we studied the lens crystallin profile of the tropical freshwater catfish Rita rita. Profiles of lens crystallins were analyzed and crystallin proteome maps of Rita rita were generated for the first time. alphaA-crystallins, member of the alpha-crystallin family, which are molecular chaperons and play crucial role in maintaining lens transparency were identified by 1- and 2-D immunoblot analysis with anti-alphaA-crystallin antibody. Two protein bands of 19-20 kDa were identified as alphaA-crystallins on 1-D immunoblots and these bands separated into 10 discrete spots on 2-D immunoblot. However, anti-alphaB-crystallin and antiphospho-alphaB-crystallin antibodies were not able to detect any immunoreactive bands on 1- and 2-D immunoblots, indicating alphaB-crystallin was either absent or present in extremely low concentration in Rita rita lens. Thus, Rita rita alpha-crystallins are more like that of the catfish Clarias batrachus and the mammal kangaroo in its alphaA- and alphaB-crystallin content (contain low amount from 5-9% of alphaB-crystallin) and unlike the dogfish, zebrafish, human, bovine and mouse alpha-crystallins (contain higher amount of alphaB-crystallin from 25% in mouse and bovine to 85% in dogfish). Results of the present study can be the baseline information for stimulating further investigation on Rita rita lens crystallins for comparative lens proteomics. Comparing and contrasting the alpha-crystallins of the dogfish and Rita rita may provide valuable information on the functional attributes of alphaA- and alphaB-isoforms, as

  14. 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

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

    PubMed

    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 [(3)H]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 [(3)H]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

  16. Extralenticular and Lenticular Aspects of Accommodation and Presbyopia in Human Versus Monkey Eyes

    PubMed Central

    Croft, Mary Ann; McDonald, Jared P.; Katz, Alexander; Lin, Ting-Li; Lütjen-Drecoll, Elke; Kaufman, Paul L.

    2013-01-01

    Purpose. To determine if the accommodative forward movements of the vitreous zonule and lens equator occur in the human eye, as they do in the rhesus monkey eye; to investigate the connection between the vitreous zonule posterior insertion zone and the posterior lens equator; and to determine which components—muscle apex width, lens thickness, lens equator position, vitreous zonule, circumlental space, and/or other intraocular dimensions, including those stated in the objectives above—are most important in predicting accommodative amplitude and presbyopia. Methods. Accommodation was induced pharmacologically in 12 visually normal human subjects (ages 19–65 years) and by midbrain electrical stimulation in 11 rhesus monkeys (ages 6–27 years). Ultrasound biomicroscopy imaged the entire ciliary body, anterior and posterior lens surfaces, and the zonule. Relevant distances were measured in the resting and accommodated eyes. Stepwise regression analysis determined which variables were the most important predictors. Results. The human vitreous zonule and lens equator move forward (anteriorly) during accommodation, and their movements decline with age, as in the monkey. Over all ages studied, age could explain accommodative amplitude, but not as well as accommodative lens thickening and resting muscle apex thickness did together. Accommodative change in distances between the vitreous zonule insertion zone and the posterior lens equator or muscle apex were important for predicting accommodative lens thickening. Conclusions. Our findings quantify the movements of the zonule and ciliary muscle during accommodation, and identify their age-related changes that could impact the optical change that occurs during accommodation and IOL function. PMID:23745002

  17. Cellulose based soft gel like actuator for reconfigurable lens array

    NASA Astrophysics Data System (ADS)

    Sadasivuni, Kishor Kumar; Yadav, Mithilesh; Gao, Xiaoyuan; Mun, Seongcheol; Kim, Jaehwan

    2014-04-01

    Reconfigurable lens is biomimetic as it mimics human eye and is a transparent actuating material that can change its curvature in the presence of external stimuli. Focus tunable, adaptive lenses provide several advantages over traditional lens assemblies in terms of compactness, cost, efficiency and flexibility. To further improve the simplicity and compact nature of adaptive lenses, we present lens system which makes use of an inline, transparent electro active polymer actuator. This paper reports the preliminary development we have achieved in reconfigurable lens systems made with cellulose nanocrystals (CNC) using the principle of Kerr effect. Preparation of the hydrophobic CNC solution as well as the optical properties of the lens has been discussed. This soft gel actuator was analyzed by measuring the electric birefringence in the pulse field of constant and sinusoidal voltage based on the use of modulation of elliptic light polarization.

  18. Reaction of tyrosine oxidation products with proteins of the lens

    PubMed Central

    Pirie, Antoinette

    1968-01-01

    Oxidation of tyrosine in the presence of bovine lens proteins leads to the formation of brown or black melanoproteins. Both tyrosinase and the oxidizing system of ferrous sulphate–ascorbic acid–EDTA are effective. The fluorescence of the lens proteins is both altered and enhanced by the tyrosine-oxidizing systems. Their fluorescence spectra resemble those of urea-insoluble proteins of human cataractous lens and of 1,2-naphthaquinone–proteins of naphthalene cataract. The lens proteins lose their thiol groups and, in acid hydrolysates of treated β-and γ-crystallins, a substance has been detected chromatographically that behaves similarly to a compound formed when 3,4-dihydroxyphenylalanine (dopa) is oxidized by tyrosinase in the presence of cysteine. Analysis and behaviour of this substance from hydrolysates of lens proteins suggest that it is a compound of cysteine and dopa. PMID:4971287

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

    PubMed

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

    2015-12-01

    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.

  20. 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)

  1. 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…

  2. 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

  3. 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. PMID:27191382

  4. 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

  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. Elevated GDF11 Is a Risk Factor for Age-Related Frailty and Disease in Humans.

    PubMed

    Glass, David J

    2016-07-12

    GDF11 was reported to decline with age and to have muscle and heart rejuvenating effects. These reports were disputed. A Cell Metabolism paper now shows that in human beings, GDF11 does not decline with age and is actually a risk factor for frailty and other morbidities (Schafer et al., 2016). PMID:27411004

  7. 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.

  8. 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. PMID:1398371

  9. 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...

  10. Canine ceroid lipofuscinosis, a model for ageing of the human isocortex.

    PubMed

    Braak, H; Braak, E; Strenge, H; Koppang, N

    1984-01-01

    In canine ceroid lipofuscinosis (one case studied), isocortical layer IIIab pyramidal cells develop spindle-shaped enlargements of their proximal axon filled with lipopigment, a feature that can be observed in juvenile and adult type of human neuronal ceroid lipofuscinosis and in normal ageing of the human isocortex as well. PMID:6479601

  11. Ultrastructure of Leydig cells in human ageing testes.

    PubMed Central

    Paniagua, R; Amat, P; Nistal, M; Martin, A

    1986-01-01

    Ultrastructural study of Leydig cells in elderly men revealed the following Leydig cell types: (1) ultrastructurally normal Leydig cells (46.2%); (2) Leydig cells either with multiple cytoplasmic or intranuclear Reinke crystals or with numerous para-crystalline inclusions (6.1%); (3) multivacuolated Leydig cells with the cytoplasm almost filled by lipid droplets (16.7%; (4) dedifferentiated Leydig cells with poor development of agranular endoplasmic reticulum and mitochondria, and increased amounts of lipofuscin granules (22.3%); and (5) bi- or trinucleate Leydig cells (8.7%) showing either a normal (2.8%) or dedifferentiated (5.9%) cytoplasm. These results suggest an involution of Leydig cells with advancing age. A correlation between the proportion of altered Leydig cells and the decrease in testosterone and increase in luteinising hormone levels could be observed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Figs. 6-7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 PMID:3693056

  12. 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

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

    PubMed

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

    2000-06-01

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

  14. Similarly Strong Purifying Selection Acts on Human Disease Genes of All Evolutionary Ages

    PubMed Central

    Cai, James J.; Borenstein, Elhanan; Chen, Rong

    2009-01-01

    A number of studies have showed that recently created genes differ from the genes created in deep evolutionary past in many aspects. Here, we determined the age of emergence and propensity for gene loss (PGL) of all human protein–coding genes and compared disease genes with non-disease genes in terms of their evolutionary rate, strength of purifying selection, mRNA expression, and genetic redundancy. The older and the less prone to loss, non-disease genes have been evolving 1.5- to 3-fold slower between humans and chimps than young non-disease genes, whereas Mendelian disease genes have been evolving very slowly regardless of their ages and PGL. Complex disease genes showed an intermediate pattern. Disease genes also have higher mRNA expression heterogeneity across multiple tissues than non-disease genes regardless of age and PGL. Young and middle-aged disease genes have fewer similar paralogs as non-disease genes of the same age. We reasoned that genes were more likely to be involved in human disease if they were under a strong functional constraint, expressed heterogeneously across tissues, and lacked genetic redundancy. Young human genes that have been evolving under strong constraint between humans and chimps might also be enriched for genes that encode important primate or even human-specific functions. PMID:20333184

  15. Analysis of cancer genomes reveals basic features of human aging and its role in cancer development

    PubMed Central

    Podolskiy, Dmitriy I.; Lobanov, Alexei V.; Kryukov, Gregory V.; Gladyshev, Vadim N.

    2016-01-01

    Somatic mutations have long been implicated in aging and disease, but their impact on fitness and function is difficult to assess. Here by analysing human cancer genomes we identify mutational patterns associated with aging. Our analyses suggest that age-associated mutation load and burden double approximately every 8 years, similar to the all-cause mortality doubling time. This analysis further reveals variance in the rate of aging among different human tissues, for example, slightly accelerated aging of the reproductive system. Age-adjusted mutation load and burden correlate with the corresponding cancer incidence and precede it on average by 15 years, pointing to pre-clinical cancer development times. Behaviour of mutation load also exhibits gender differences and late-life reversals, explaining some gender-specific and late-life patterns in cancer incidence rates. Overall, this study characterizes some features of human aging and offers a mechanism for age being a risk factor for the onset of cancer. PMID:27515585

  16. Genetic determination of telomere size in humans: A twin study of three age groups

    SciTech Connect

    Slagboom, P.E.; Droog, S.; Boomsma, D.I.

    1994-11-01

    Reduction of telomere length has been postulated to be a casual factor in cellular aging. Human telomeres terminate in tandemly arranged repeat arrays consisting of the (TTAGGG) motif. The length of these arrays in cells from human mitotic tissues is inversely related to the age of the donor, indicating telomere reduction with age. In addition to telemore length differences between different age cohorts, considerable variation is present among individuals of the same age. To investigate whether this variation can be ascribed to genetic influences, we have measured the size of terminal restriction fragments (TRFs) in HaeIII-digested genomic DNA from 123 human MZ and DZ twin pairs 2-95 years of age. The average rate of telomere shortening was 31 bp/year, which is similar to that observed by others. Statistical analysis in 115 pairs 2-63 years of age indicates a 78% heritability for mean TRF length in this age cohort. The individual differences in mean TRF length in blood, therefore, seem to a large extent to be genetically determined. 24 refs., 4 figs., 2 tabs.

  17. 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

  18. The effect of plant aging on equipment qualification and human performance issues related to license renewal

    SciTech Connect

    Gunther, W.E.; Higgins, J.C.; Aggarwal, S.K.

    1991-12-31

    The aging of nuclear power plants is one of the most important issues facing the nuclear industry worldwide. Aging encompasses as forms of degradation to nuclear power plant components, systems, and structures that result from exposure to environmental conditions or from operational stresses. Both the degradation from aging and actions taken to address the aging, such as increased maintenance and testing, can significantly impact human performance in the plant. Research into the causes and effects of aging as obtained through the assessment of operating experience and testing have raised questions regarding the adequacy of existing industry standards for addressing the concerns raised by this research. This paper discusses these issues, with particular emphasis in the area of equipment qualification and human performance.

  19. 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.

  20. Hypothesis: is yeast a clock model to study the onset of humans aging phenotypes?

    PubMed

    Mazzoni, Cristina; Mangiapelo, Eleonora; Palermo, Vanessa; Falcone, Claudio

    2012-01-01

    In this paper we report the growth and aging of yeast colonies derived from single cells isolated by micromanipulation and seeded one by one on separated plates to avoid growth interference by surrounding colonies. We named this procedure clonal life span, and it could represent a third way of studying aging together with the replicative life span and chronological life span. In this study we observed over time the formation of cell mass similar to the human "senile warts" (seborrheic keratoses), the skin lesions that often appear after 30 years of life and increase in number and size over the years. We observed that similar signs of aging appear in yeast colonies after about 27 days of growth and increase during aging. In this respect we hypothesize to use yeast as a clock to study the onset of human aging phenotypes.

  1. Increased excitability of somatosensory cortex in aged humans is associated with impaired tactile acuity.

    PubMed

    Lenz, Melanie; Tegenthoff, Martin; Kohlhaas, Karsten; Stude, Philipp; Höffken, Oliver; Gatica Tossi, Mario A; Kalisch, Tobias; Kowalewski, Rebecca; Dinse, Hubert R

    2012-02-01

    Aging affects all levels of neural processing, including changes of intracortical inhibition and cortical excitability. Paired-pulse stimulation, the application of two stimuli in close succession, is a useful tool to investigate cortical excitability in humans. The paired-pulse behavior is characterized by the second response being significantly suppressed at short stimulus onset asynchronies. While in rat somatosensory cortex, intracortical inhibition has been demonstrated to decline with increasing age, data from human motor cortex of elderly subjects are controversial and there are no data for the human somatosensory cortex (SI). Moreover, behavioral implications of age-related changes of cortical excitability remain elusive. We therefore assessed SI excitability by combining paired-pulse median nerve stimulation with recording somatosensory evoked potentials in 138 healthy subjects aged 17-86 years. We found that paired-pulse suppression was characterized by substantial interindividual variability, but declined significantly with age, confirming reduced intracortical inhibition in elderly subjects. To link the age-related increase of cortical excitability to perceptual changes, we measured tactile two-point discrimination in a subsample of 26 aged participants who showed either low or high paired-pulse suppression. We found that tactile performance was particularly impaired in subjects showing markedly enhanced cortical excitability. Our data demonstrate that paired-pulse suppression of human SI is significantly reduced in older adults, and that age-related enhancement of cortical excitability correlates with degradation of tactile perception. These findings indicate that cortical excitability constitutes an important mechanism that links age-related neurophysiological changes to behavioral alterations in humans.

  2. Morphological Characteristics of the Cartilaginous Tissue of Human Auricle in Different Age Periods.

    PubMed

    Novoselov, V P; Savchenko, S V; Pyatkova, E V; Nadeev, A P; Ageeva, T A; Chikinev, Yu V; Polyakevich, A S

    2016-04-01

    A complex morphological study of the auricle to determine the human age was performed by evaluating the metric sizes between fixed points in each auricle with axial guidelines. The auricular elastic cartilage in different age periods was characterized by thickening of the cartilaginous plate, different mature and immature cartilage zone ratio, variations in the volume density of the intercellular substance and elastic fibers, and change in the numerical density of individual chondrocytes and isogroups. Aggrecan content in the cartilage was shown to increase in different age periods. Age-related structural changes in the auricular cartilage expand the possibilities of forensic medical examination and hold much promise for the identification of personality.

  3. Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells

    PubMed Central

    Elanchezhian, R; Palsamy, P; Madson, C J; Mulhern, M L; Lynch, D W; Troia, A M; Usukura, J; Shinohara, T

    2012-01-01

    Aging is enhanced by hypoxia and oxidative stress. As the lens is located in the hypoglycemic environment under hypoxia, aging lens with diabetes might aggravate these stresses. This study was designed to examine whether low glucose under hypoxic conditions induces the unfolded protein response (UPR), and also if the UPR then generates the reactive oxygen species (ROS) in lens epithelial cells (LECs). The UPR was activated within 1 h by culturing the human LECs (HLECs) and rat LECs in <1.5 mM glucose under hypoxic conditions. These conditions also induced the Nrf2-dependent antioxidant-protective UPR, production of ROS, and apoptosis. The rat LECs located in the anterior center region were the least susceptible to the UPR, whereas the proliferating LECs in the germinative zone were the most susceptible. Because the cortical lens fiber cells are differentiated from the LECs after the onset of diabetes, we suggest that these newly formed cortical fibers have lower levels of Nrf2, and are then oxidized resulting in cortical cataracts. Thus, low glucose and oxygen conditions induce the UPR, generation of ROS, and expressed the Nrf2 and Nrf2-dependent antioxidant enzymes at normal levels. But these cells eventually lose reduced glutathione (GSH) and induce apoptosis. The results indicate a new link between hypoglycemia under hypoxia and impairment of HLEC functions. PMID:22513875

  4. 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.

  5. 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.

  6. [Development, human rights and woman's condition: a new age].

    PubMed

    Isaacs, S L

    1989-06-01

    After World War II (WWII) concern grew about the economic and social development of Third World countries. Most countries in Africa, Asia and the Middle East were European colonies while Latin America, even though independent was completely dominated by the US. These countries are characterized by: 1) a poor majority ruled by a small rich minority; 2) large rural populations migrating to the cities resulting in bottlenecks and unemployment; 3) bad health status with deteriorating nutritional states; 4) large families; 5) low levels of education (2/3 of the women in the world are illiterate and 90% live in 17 countries); 5) high levels of corruption in public positions; 6) governments ruled by a military dictator; 7) women in the lowest positions with limited legal rights. After WWII the Marshall Plan was instituted in developing countries (LDCs) to provide economic aid to development a model that used per capita income to measure a country's progress. During the 70's and 80's this model was questioned and more emphasis was put on the need for social and institutional development before investing in economic development. The World Bank and USAID have been promoting the role of the public sector, a strategy that has lowered inflation but has also affected the poor in many countries. For example, infant mortality in Brazil is higher now than 10 years ago. A wise development policy should recognize the need of LDCs to develop their own models while emphasizing agricultural development rather than industrial. Development is never accomplished until every citizen participates in their community. Improving the status of women is not only a human right but a high priority in achieving development. Women in LDCs only have partial rights--they cannot own land, nor inherit, and are not given any credit. Development is not only increasing the per capita income, it includes improving health, education, nutrition, and the quality of life of all its citizens. International law

  7. 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

    2008-12-01

    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.

  8. Aging and DNA damage in humans: a meta-analysis study

    PubMed Central

    Soares, Jorge Pinto; Cortinhas, António; Bento, Teresa; Leitão, José Carlos; Collins, Andrew R.; Gaivã, Isabel; Mota, Maria Paula

    2014-01-01

    Age-related DNA damage is regarded as one of the possible explanations of aging. Although a generalized idea about the accumulation of DNA damage with age exists, results found in the literature are inconsistent. To better understand the question of age-related DNA damage in humans and to identify possible moderator variables, a meta-analysis was conducted. Electronic databases and bibliographies for studies published since 2004 were searched. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for age-related DNA damage were calculated in a random-effects model. A total of 76 correlations from 36 studies with 4676 participants were included. Based on our analysis, a correlation between age and DNA damage was found (r = 0.230, p = 0.000; 95% confidence interval = 0.111 - 0.342). The test for heterogeneity of variance indicates that the study´s results are significantly high (Q (75) = 1754.831, p = 0.000). Moderator variables such as smoking habits, technique used, and the tissue/sample analyzed, are shown to influence age-related DNA damage (p=0.026; p=0.000; p=0.000, respectively). Nevertheless, sex did not show any influence on this relation (p=0.114). In conclusion, this meta-analysis showed an association between age and DNA damage in humans. It was also found that smoking habits, the technique used, and tissue/sample analyzed, are important moderator variables in age-related DNA damage. PMID:25140379

  9. Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts

    PubMed Central

    Huh, Christine J; Zhang, Bo; Victor, Matheus B; Dahiya, Sonika; Batista, Luis FZ; Horvath, Steve; Yoo, Andrew S

    2016-01-01

    Aging is a major risk factor in many forms of late-onset neurodegenerative disorders. The ability to recapitulate age-related characteristics of human neurons in culture will offer unprecedented opportunities to study the biological processes underlying neuronal aging. Here, we show that using a recently demonstrated microRNA-based cellular reprogramming approach, human fibroblasts from postnatal to near centenarian donors can be efficiently converted into neurons that maintain multiple age-associated signatures. Application of an epigenetic biomarker of aging (referred to as epigenetic clock) to DNA methylation data revealed that the epigenetic ages of fibroblasts were highly correlated with corresponding age estimates of reprogrammed neurons. Transcriptome and microRNA profiles reveal genes differentially expressed between young and old neurons. Further analyses of oxidative stress, DNA damage and telomere length exhibit the retention of age-associated cellular properties in converted neurons from corresponding fibroblasts. Our results collectively demonstrate the maintenance of age after neuronal conversion. DOI: http://dx.doi.org/10.7554/eLife.18648.001 PMID:27644593

  10. Rejuvenation of Gene Expression Pattern of Aged Human Skin by Broadband Light Treatment: A Pilot Study

    PubMed Central

    Chang, Anne Lynn S; Bitter, Patrick H; Qu, Kun; Lin, Meihong; Rapicavoli, Nicole A; Chang, Howard Y

    2013-01-01

    Studies in model organisms suggest that aged cells can be functionally rejuvenated, but whether this concept applies to human skin is unclear. Here we apply 3′-end sequencing for expression quantification (“3-seq”) to discover the gene expression program associated with human photoaging and intrinsic skin aging (collectively termed “skin aging”), and the impact of broadband light (BBL) treatment. We find that skin aging was associated with a significantly altered expression level of 2,265 coding and noncoding RNAs, of which 1,293 became “rejuvenated” after BBL treatment; i.e., they became more similar to their expression level in youthful skin. Rejuvenated genes (RGs) included several known key regulators of organismal longevity and their proximal long noncoding RNAs. Skin aging is not associated with systematic changes in 3′-end mRNA processing. Hence, BBL treatment can restore gene expression pattern of photoaged and intrinsically aged human skin to resemble young skin. In addition, our data reveal, to our knowledge, a previously unreported set of targets that may lead to new insights into the human skin aging process. PMID:22931923

  11. Functional modular contact lens

    NASA Astrophysics Data System (ADS)

    Shum, Angela J.; Cowan, Melissa; Lähdesmäki, Ilkka; Lingley, Andrew; Otis, Brian; Parviz, Babak A.

    2009-08-01

    Tear fluid offers a potential route for non-invasive sensing of physiological parameters. Utilization of this potential depends on the ability to manufacture sensors that can be placed on the surface of the eye. A contact lens makes a natural platform for such sensors, but contact lens polymers present a challenge for sensor fabrication. This paper describes a microfabrication process for constructing sensors that can be integrated into the structure of a functional contact lens in the future. To demonstrate the capabilities of the process, an amperometric glucose sensor was fabricated on a polymer substrate. The sensor consists of platinum working and counter electrodes, as well as a region of indium-tin oxide (ITO) for glucose oxidase immobilization. An external silver-silver chloride electrode was used as the reference electrode during the characterization experiments. Sensor operation was validated by hydrogen peroxide measurements in the 10- 20 μM range and glucose measurements in the 0.125-20 mM range.

  12. Polarization sensitive changes in the human macula associated with normal aging and age-related macular degeneration

    NASA Astrophysics Data System (ADS)

    VanNasdale, Dean Allan, Jr.

    2011-12-01

    The human macula occupies a relatively small, but crucial retinal area, as it is the location responsible for our most acute spatial vision and best color discrimination. Localizing important landmarks in the retina is difficult even in normal eyes where morphological inter-individual variability is high. This becomes even more challenging in the presence of sight-threatening pathology. With respect to the human macula, there remains a significant gap in the understanding of normal structure and function. Even less is known about the pathological mechanisms that occur in sight-threatening diseases including age-related macular degeneration. Because relatively little is known about normal aging changes, it is also difficult to differentiate those changes from changes associated with retinal disease. To better understand normal and pathological changes in the macula, imaging techniques using specific optical signatures are required. Structural features in the macula can be distinguished based on their intrinsic properties using specific light/tissue interactions. Because of the high degree of structural regularity in the macula, polarization sensitive imaging is potentially a useful tool for evaluating the morphology and integrity of the cellular architecture for both normal individuals and those affected by disease. In our investigations, we used polarization sensitive imaging to determining normal landmarks that are important clinically and for research investigations. We found that precision and accuracy in localizing the central macula was greatly improved through the use of polarization sensitive imaging. We also found that specific polarization alterations can be used to demonstrate systematic changes as a function of age, disproportionately affecting the central macular region. When evaluating patients with age-related macular degeneration, we found that precision and accuracy of localizing the central macula was also improved, even when significant pathology

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  14. Signal-enhancement reflective pulse oximeter with Fresnel lens

    NASA Astrophysics Data System (ADS)

    Chung, Shuang-Chao; Sun, Ching-Cherng

    2016-09-01

    In this paper, a new reflective pulse oximeter is proposed and demonstrated with implanting a Fresnel lens, which enhances the reflected signal. An optical simulation model incorporated with human skin characteristics is presented to evaluate the capability of the Fresnel lens. In addition, the distance between the light emitting diode and the photodiode is optimized. Compared with the other reflective oximeters, the reflected signal light detected by the photodiode is enhanced to more than 140%.

  15. Detection of mucus glycoconjugates in human conjunctiva by using the lectin-colloidal gold technique in TEM. III. A quantitative study in asymptomatic contact lens wearers.

    PubMed

    Versura, P; Maltarello, M C; Cellini, M; Marinelli, F; Caramazza, R; Laschi, R

    1987-12-01

    We characterized the mucus glycoconjugates produced by goblet and non-goblet epithelial cells in asymptomatic contact lens (CL) wearers. We employed four lectins (proteins of vegetal origin which specifically recognize glycosidic residues: WGA, PNA, SBA and ConA) conjugated with colloidal gold as ultrastructural marker, at Transmission Electron Microscopy. A computerized quantitative analysis was carried out in order to compare the results from the CL wearers to those from the control patients. Goblet cells produce different amount of glycosidic residues, in particular, a significant decrease in the distribution of sialic acid, N-acetylglucosamine, N-acetylgalactosamine, galactose-N-acetylgalactosamine and mannose was observed. The content of glycosidic residues in the mucus vesicles of the non-goblet epithelial cells appeared unchanged as to the normal situation. We speculate that the CL could possibly contribute to the failure of the tear film stability by altering the production of mucus.

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

    PubMed Central

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

    2015-01-01

    Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1α and nuclear lamina-heterochromatin anchoring protein LAP2β. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging. PMID:25931448

  17. The impact of age at death on the lag time of radiocarbon values in human bone.

    PubMed

    Ubelaker, Douglas H; Thomas, Christian; Olson, Jacqueline E

    2015-06-01

    Analysis of modern bomb-pulse radiocarbon in human bone offers data needed to interpret the post-mortem interval in skeletonized human remains recovered from forensic contexts. Radiocarbon analysis of different tissues with distinct rates of remodeling allows proper placement of the values on the modern bomb-curve. However, the lag time between the date of intercept on the curve and the actual death date is largely affected by the age at death. Published data on radiocarbon analysis of individuals of known age at death and death dates indicate that this lag time increases with age until about 60 years. The lag time documented for each decade of life can be used to compensate for this age-related factor and increase the accuracy of interpretation of the death date. While this method could be greatly improved by original research with a larger sample size, this study provides an adequate point from which to launch further investigations into the subject.

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

    NASA Astrophysics Data System (ADS)

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

    2005-01-01

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

  19. Aging Shapes the Population-Mean and -Dispersion of Gene Expression in Human Brains

    PubMed Central

    Brinkmeyer-Langford, Candice L.; Guan, Jinting; Ji, Guoli; Cai, James J.

    2016-01-01

    Human aging is associated with cognitive decline and an increased risk of neurodegenerative disease. Our objective for this study was to evaluate potential relationships between age and variation in gene expression across different regions of the brain. We analyzed the Genotype-Tissue Expression (GTEx) data from 54 to 101 tissue samples across 13 brain regions in post-mortem donors of European descent aged between 20 and 70 years at death. After accounting for the effects of covariates and hidden confounding factors, we identified 1446 protein-coding genes whose expression in one or more brain regions is correlated with chronological age at a false discovery rate of 5%. These genes are involved in various biological processes including apoptosis, mRNA splicing, amino acid biosynthesis, and neurotransmitter transport. The distribution of these genes among brain regions is uneven, suggesting variable regional responses to aging. We also found that the aging response of many genes, e.g., TP37 and C1QA, depends on individuals' genotypic backgrounds. Finally, using dispersion-specific analysis, we identified genes such as IL7R, MS4A4E, and TERF1/TERF2 whose expressions are differentially dispersed by aging, i.e., variances differ between age groups. Our results demonstrate that age-related gene expression is brain region-specific, genotype-dependent, and associated with both mean and dispersion changes. Our findings provide a foundation for more sophisticated gene expression modeling in the studies of age-related neurodegenerative diseases. PMID:27536236

  20. Sexual dimorphism of facial appearance in ageing human adults: A cross-sectional study.

    PubMed

    Mydlová, Miriama; Dupej, Ján; Koudelová, Jana; Velemínská, Jana

    2015-12-01

    In the forensic sciences, knowledge of facial ageing is very important in searching for both dead and living individuals. Ageing estimations typically model the biological profile, which can be compared to missing persons. The main goals of this current study were to construct ageing trajectories for adult human faces of both sexes and evaluate sexual dimorphism in relation to static allometry. Our study was based on the analysis of three-dimensional facial surface models of 194 individuals 20-80 years of age. The evaluation consisted of a dense correspondence analysis of facial scans and multivariate statistics. It was shown that both age and sex have a significant influence on facial form and shape. Male features included a longer face, with more protruded foreheads, eyebrow ridges and nose, including the region under the upper lip and mandible region, but more retruded cheeks compared to females. Ageing in both sexes shared common traits, such as more pronounced roundness of the face (rectangular in males), decreased facial convexity, increased visibility of skin folds and wrinkles connected with the loss of skin elasticity, and soft tissue stretching, especially in the orbital area and lower face; however, male faces exhibited more intense ageing changes. The above-mentioned sexual dimorphic traits tended to diminish in the elderly age category, though overall sexual dimorphism was heightened with age. The static allometric relationships between size and form or shape were similar in both sexes, except that the larger faces of elderly males displayed more intensive ageing changes.

  1. Sexual dimorphism of facial appearance in ageing human adults: A cross-sectional study.

    PubMed

    Mydlová, Miriama; Dupej, Ján; Koudelová, Jana; Velemínská, Jana

    2015-12-01

    In the forensic sciences, knowledge of facial ageing is very important in searching for both dead and living individuals. Ageing estimations typically model the biological profile, which can be compared to missing persons. The main goals of this current study were to construct ageing trajectories for adult human faces of both sexes and evaluate sexual dimorphism in relation to static allometry. Our study was based on the analysis of three-dimensional facial surface models of 194 individuals 20-80 years of age. The evaluation consisted of a dense correspondence analysis of facial scans and multivariate statistics. It was shown that both age and sex have a significant influence on facial form and shape. Male features included a longer face, with more protruded foreheads, eyebrow ridges and nose, including the region under the upper lip and mandible region, but more retruded cheeks compared to females. Ageing in both sexes shared common traits, such as more pronounced roundness of the face (rectangular in males), decreased facial convexity, increased visibility of skin folds and wrinkles connected with the loss of skin elasticity, and soft tissue stretching, especially in the orbital area and lower face; however, male faces exhibited more intense ageing changes. The above-mentioned sexual dimorphic traits tended to diminish in the elderly age category, though overall sexual dimorphism was heightened with age. The static allometric relationships between size and form or shape were similar in both sexes, except that the larger faces of elderly males displayed more intensive ageing changes. PMID:26548377

  2. THE OPTIMAL GRAVITATIONAL LENS TELESCOPE

    SciTech Connect

    Surdej, J.; Hanot, C.; Sadibekova, T.; Delacroix, C.; Habraken, S.; Coleman, P.; Dominik, M.; Le Coroller, H.; Mawet, D.; Quintana, H.; Sluse, D.

    2010-05-15

    Given an observed gravitational lens mirage produced by a foreground deflector (cf. galaxy, quasar, cluster, ...), it is possible via numerical lens inversion to retrieve the real source image, taking full advantage of the magnifying power of the cosmic lens. This has been achieved in the past for several remarkable gravitational lens systems. Instead, we propose here to invert an observed multiply imaged source directly at the telescope using an ad hoc optical instrument which is described in the present paper. Compared to the previous method, this should allow one to detect fainter source features as well as to use such an optimal gravitational lens telescope to explore even fainter objects located behind and near the lens. Laboratory and numerical experiments illustrate this new approach.

  3. Miniature hybrid optical imaging lens

    DOEpatents

    Sitter, D.N. Jr.; Simpson, M.L.

    1997-10-21

    A miniature lens system that corrects for imaging and chromatic aberrations is disclosed, the lens system being fabricated from primarily commercially-available components. A first element at the input to a lens housing is an aperture stop. A second optical element is a refractive element with a diffractive element closely coupled to, or formed a part of, the rear surface of the refractive element. Spaced closely to the diffractive element is a baffle to limit the area of the image, and this is closely followed by a second refractive lens element to provide the final correction. The image, corrected for aberrations exits the last lens element to impinge upon a detector plane were is positioned any desired detector array. The diffractive element is fabricated according to an equation that includes, as variables, the design wavelength, the index of refraction and the radius from an optical axis of the lens system components. 2 figs.

  4. Miniature hybrid optical imaging lens

    DOEpatents

    Sitter, Jr., David N.; Simpson, Marc L.

    1997-01-01

    A miniature lens system that corrects for imaging and chromatic aberrations, the lens system being fabricated from primarily commercially-available components. A first element at the input to a lens housing is an aperture stop. A second optical element is a refractive element with a diffractive element closely coupled to, or formed a part of, the rear surface of the refractive element. Spaced closely to the diffractive element is a baffle to limit the area of the image, and this is closely followed by a second refractive lens element to provide the final correction. The image, corrected for aberrations exits the last lens element to impinge upon a detector plane were is positioned any desired detector array. The diffractive element is fabricated according to an equation that includes, as variables, the design wavelength, the index of refraction and the radius from an optical axis of the lens system components.

  5. Endothelial ischemia-reperfusion injury in humans: association with age and habitual exercise

    PubMed Central

    Umpierre, Daniel; Harrison, Michelle L.; Lin, Hsin-Fu; Tarumi, Takashi; Renzi, Christopher P.; Dhindsa, Mandeep; Hunter, Stacy D.; Tanaka, Hirofumi

    2011-01-01

    Advancing age is a major risk factor for coronary artery disease. Endothelial dysfunction accompanied by increased oxidative stress and inflammation with aging may predispose older arteries to greater ischemia-reperfusion (I/R) injury. Because coronary artery ischemia cannot be induced safely, the effects of age and habitual endurance exercise on endothelial I/R injury have not been determined in humans. Using the brachial artery as a surrogate model of the coronary arteries, endothelial function, assessed by brachial artery flow-mediated dilation (FMD), was measured before and after 20 min of continuous forearm occlusion in young sedentary (n = 10, 24 ± 2 yr) and middle-aged (n = 9, 48 ± 2 yr) sedentary adults to gain insight into the effects of primary aging on endothelial I/R injury. Young (n = 9, 25 ± 1 yr) and middle-aged endurance-trained (n = 9, 50 ± 2 yr) adults were also studied to determine whether habitual exercise provides protection from I/R injury. Fifteen minutes after ischemic injury, FMD decreased significantly by 37% in young sedentary, 35% in young endurance-trained, 68% in middle-aged sedentary, and 50% in middle-aged endurance-trained subjects. FMD returned to baseline levels within 30 min in young sedentary and endurance-trained subjects but remained depressed in middle-aged sedentary and endurance-trained subjects. Circulating markers of antioxidant capacity and inflammation were not related to FMD. In conclusion, advancing age is associated with a greater magnitude and delayed recovery from endothelial I/R injury in humans. Habitual endurance exercise may provide partial protection to the endothelium against this form of I/R injury with advancing age. PMID:21239631

  6. Thin Film Evolution Over a Thin Porous Layer: Modeling a Tear Film on a Contact Lens

    NASA Astrophysics Data System (ADS)

    Anderson, Daniel; Nong, Kumnit

    2010-11-01

    We examine a mathematical model that describes the behavior of the pre-contact lens tear film of a human eye. Our work examines the effect of contact lens thickness and lens permeability and slip on the film dynamics. A mathematical model for the evolution of the tear film is derived using a lubrication approximation applied to the hydrodynamic equations of motion in the fluid film and the porous layer. The model is a nonlinear fourth order partial differential equation subject to boundary conditions and an initial condition for post-blink film evolution. We find that increasing the lens thickness, permeability and slip all contribute to an increase in the film thinning rate although for parameter values typical for contact lens wear these modifications are minor. The presence of the contact lens can, however, fundamentally change the nature of the rupture dynamics as the inclusion of the porous lens leads to rupture in finite time rather than infinite time.

  7. Physical changes in human meibum with age as measured by infrared spectroscopy.

    PubMed

    Borchman, Douglas; Foulks, Gary N; Yappert, Marta C; Kakar, Shelly; Podoll, Nathan; Rychwalski, Paul; Schwietz, Eric

    2010-01-01

    Both lipids and mucins contribute to the stability of the tear film and lipids may inhibit tears from evaporating. Younger people have lower lipid viscosity, higher lipid volume, and a lower rate of tear evaporation. Since age-related changes in human meibum composition and conformation have never been investigated, as a basis for the study of lipid-associated changes with meibomian gland dysfunction, we used the power of infrared spectroscopy to characterize hydrocarbon chain conformation and packing in meibum from humans without dry eye symptoms in relation to age and sex. Meibum from normal human donors ranging in age from 3 to 88 years was studied. Meibum phase transitions were quantified by fitting them to a 4-parameter 2-state sigmoidal equation. Human meibum order and phase transition temperatures decrease with age and this trend may be attributed to lipid compositional changes. If meibum has the same thermodynamic properties on the surface of the tears as it does on the lid margin, a decrease in lipid-lipid interaction strength with increasing age could decrease the stability of tears since lipid-lipid interactions on the tear surface must be broken for the tear film to break up. This study also serves as a foundation to examine meibum conformational differences in meibum from people with meibomian gland dysfunction.

  8. Developing Humanities Collections in the Digital Age: Exploring Humanities Faculty Engagement with Electronic and Print Resources

    ERIC Educational Resources Information Center

    Kachaluba, Sarah Buck; Brady, Jessica Evans; Critten, Jessica

    2014-01-01

    This article is based on quantitative and qualitative research examining humanities scholars' understandings of the advantages and disadvantages of print versus electronic information resources. It explores how humanities' faculty members at Florida State University (FSU) use print and electronic resources, as well as how they perceive these…

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

    PubMed

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

    1997-11-01

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

  10. Dispersion-compensated Fresnel lens

    DOEpatents

    Johnson, K.C.

    1992-11-03

    A transmission grating is used to reduce chromatic aberration in a Fresnel lens, wherein the lens chromatic dispersion is offset and substantially canceled by the grating's diffraction-induced dispersion. The grating comprises a Fresnel-type pattern of microscopic facets molded directly into the lens surface. The facets would typically have a profile height of around 4[times]10[sup [minus]5] inch and a profile width of at least 10[sup [minus]3] inch. In its primary intended application, the invention would function to improve the optical performance of a Fresnel lens used to concentrate direct sunlight. 10 figs.

  11. Dispersion-compensated fresnel lens

    DOEpatents

    Johnson, Kenneth C.

    1992-01-01

    A transmission grating is used to reduce chromatic aberration in a Fresnel lens, wherein the lens chromatic dispersion is offset and substantially canceled by the grating's diffraction-induced dispersion. The grating comprises a Fresnel-type pattern of microscopic facets molded directly into the lens surface. The facets would typically have a profile height of around 4.multidot.10.sup.-5 inch and a profile width of at least 10.sup.-3 inch. In its primary intended application, the invention would function to improve the optical performance of a Fresnel lens used to concentrate direct sunlight.

  12. Challenges of using dielectric elastomer actuators to tune liquid lens

    NASA Astrophysics Data System (ADS)

    Keong, Gih-Keong; La, Thanh-Giang; Shiau, Li-Lynn; Tan, Adrian W. Y.

    2014-03-01

    Recently, dielectric elastomer actuators (DEAs) have been adopted to tune liquid membrane lens, just like ciliary muscles do to the lens in human eye. However, it faces some challenges, such as high stress, membrane puncture, high driving voltage requirement, and limited focus distance (not more than 707cm), that limit its practical use. The design problem gets more complex as the liquid lens shares the same elastomeric membrane as the DEA. To address these challenges, we separate DEA from the lens membrane. Instead, a liquid-immersed DEA, which is safe from terminal failure, is used as a diaphragm pump to inflate or deflate the liquid lens by hydraulic pressure. This opens up the possibility that the DEA can be thinned down and stacked up to reduce the driving voltage, independent of the lens membrane thickness. Preliminary study showed that our 8-mm-diameter tunable lens can focus objects in the range of 15cm to 50cm with a small driving voltage of 1.8kV. Further miniaturization of DEA could achieve a driving voltage less than 1kV.

  13. Comparison of oxime reactivation and aging of nerve agent-inhibited monkey and human acetylcholinesterases.

    PubMed

    Luo, Chunyuan; Tong, Min; Maxwell, Donald M; Saxena, Ashima

    2008-09-25

    Non-human primates are valuable animal models that are used for the evaluation of nerve agent toxicity as well as antidotes and results from animal experiments are extrapolated to humans. It has been demonstrated that the efficacy of an oxime primarily depends on its ability to reactivate nerve agent-inhibited acetylcholinesterase (AChE). If the in vitro oxime reactivation of nerve agent-inhibited animal AChE is similar to that of human AChE, it is likely that the results of an in vivo animal study will reliably extrapolate to humans. Therefore, the goal of this study was to compare the aging and reactivation of human and different monkey (Rhesus, Cynomolgus, and African Green) AChEs inhibited by GF, GD, and VR. The oximes examined include the traditional oxime 2-PAM, two H-oximes HI-6 and HLo-7, and the new candidate oxime MMB4. Results indicate that oxime reactivation of all three monkey AChEs was very similar to human AChE. The maximum difference in the second-order reactivation rate constant between human and three monkey AChEs or between AChEs from different monkey species was 5-fold. Aging rate constants of GF-, GD-, and VR-inhibited monkey AChEs were very similar to human AChE except for GF-inhibited monkey AChEs, which aged 2-3 times faster than the human enzyme. The results of this study suggest that all three monkey species are suitable animal models for nerve agent antidote evaluation since monkey AChEs possess similar biochemical/pharmacological properties to human AChE.

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

    SciTech Connect

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

    1983-03-30

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

  15. Age-related changes in human posture control: Motor coordination tests

    NASA Technical Reports Server (NTRS)

    Peterka, R. J.; Black, F. O.

    1989-01-01

    Postural responses to support surface displacements were measured in 214 normal human subjects ranging in age from 7 to 81 years. Motor tests measured leg muscle Electromyography (EMG) latencies, body sway, and the amplitude and timing of changes in center of pressure displacements in response to sudden forward and backward horizontal translations of the support surface upon which the subjects stood. There were small increases in both EMG latencies and the time to reach the peak amplitude of center of pressure responses with increasing age. The amplitude of center of pressure responses showed little change with age if the amplitude measures were normalized by a factor related to subject height. In general, postural responses to sudden translations showed minimal changes with age, and all age related trends which were identified were small relative to the variability within the population.

  16. Human neuromuscular structure and function in old age: A brief review

    PubMed Central

    Power, Geoffrey A.; Dalton, Brian H.; Rice, Charles L.

    2016-01-01

    Natural adult aging is associated with many functional impairments of the human neuromuscular system. One of the more observable alterations is the loss of contractile muscle mass, termed sarcopenia. The loss of muscle mass occurs primarily due to a progressive loss of viable motor units, and accompanying atrophy of remaining muscle fibers. Not only does the loss of muscle mass contribute to impaired function in old age, but alterations in fiber type and myosin heavy chain isoform expression also contribute to weaker, slower, and less powerful contracting muscles. This review will focus on motor unit loss associated with natural adult aging, age-related fatigability, and the age-related differences in strength across contractile muscle actions. PMID:27011872

  17. 3 Year simvastatin treatment and lens nuclear back scattering

    PubMed Central

    Qian, W.; Soderberg, P.; Chen, E.; Magnius, K.; Philipson, B.

    2000-01-01

    AIM—To determine if 3 year treatment of hypercholesterolaemia with simvastatin causes an increase of lens nuclear back scattering.
METHODS—160 patients with hypercholesterolaemia in the Scandinavian Simvastatin Survival Study (4S) were followed for 3 years. Half (80) of the patients took simvastatin and half (80) received placebo. The lens was photographed with a Topcon SL-45 slit lamp camera at the beginning and at 1 year intervals. A common lens nuclear area was used for measuring lens nuclear back scattering.
RESULTS—Nuclear back scattering increased with age and there was more pronounced scattering in women than in men. Lens nuclear back scattering did not differ significantly between the simvastatin and placebo groups, but the power was low (0.2). Lens nuclear back scattering increased during the study period independently of baseline back scattering, age, and sex for both groups.
CONCLUSION—Although no significant difference was found between the simvastatin and placebo groups, the currently available data are insufficient for exclusion of the possibility that taking simvastatin during a 3 year period increases nuclear back scattering. However, a possible minor increase of nuclear back scattering is clinically irrelevant considering known beneficial effects of simvastatin on coronary heart disease.

 PMID:10781516

  18. Human Age Estimation Method Robust to Camera Sensor and/or Face Movement

    PubMed Central

    Nguyen, Dat Tien; Cho, So Ra; Pham, Tuyen Danh; Park, Kang Ryoung

    2015-01-01

    Human age can be employed in many useful real-life applications, such as customer service systems, automatic vending machines, entertainment, etc. In order to obtain age information, image-based age estimation systems have been developed using information from the human face. However, limitations exist for current age estimation systems because of the various factors of camera motion and optical blurring, facial expressions, gender, etc. Motion blurring can usually be presented on face images by the movement of the camera sensor and/or the movement of the face during image acquisition. Therefore, the facial feature in captured images can be transformed according to the amount of motion, which causes performance degradation of age estimation systems. In this paper, the problem caused by motion blurring is addressed and its solution is proposed in order to make age estimation systems robust to the effects of motion blurring. Experiment results show that our method is more efficient for enhancing age estimation performance compared with systems that do not employ our method. PMID:26334282

  19. Human Age Estimation Method Robust to Camera Sensor and/or Face Movement.

    PubMed

    Nguyen, Dat Tien; Cho, So Ra; Pham, Tuyen Danh; Park, Kang Ryoung

    2015-01-01

    Human age can be employed in many useful real-life applications, such as customer service systems, automatic vending machines, entertainment, etc. In order to obtain age information, image-based age estimation systems have been developed using information from the human face. However, limitations exist for current age estimation systems because of the various factors of camera motion and optical blurring, facial expressions, gender, etc. Motion blurring can usually be presented on face images by the movement of the camera sensor and/or the movement of the face during image acquisition. Therefore, the facial feature in captured images can be transformed according to the amount of motion, which causes performance degradation of age estimation systems. In this paper, the problem caused by motion blurring is addressed and its solution is proposed in order to make age estimation systems robust to the effects of motion blurring. Experiment results show that our method is more efficient for enhancing age estimation performance compared with systems that do not employ our method. PMID:26334282

  20. Pentosidine Accumulation in Human Oocytes and Their Correlation to Age-Related Apoptosis

    PubMed Central

    Matsumine, Miki; Shibata, Noriyuki; Ishitani, Ken; Kobayashi, Makio; Ohta, Hiroaki

    2008-01-01

    Age-related atresia of ovarian follicles is characterized by apoptosis of the constituent cells. Recent studies have indicated that dysfunction of the proteasome and endoplasmic reticulum and subsequent apoptosis in the presence of oxidative stress have relevance to aging. The aim of this study was to assess the involvement of these processes in age-related follicular atresia. Formalin-fixed, paraffin-embedded sections of ovaries obtained at surgery from 74 women (age: 21–54 y) were examined with the terminal deoxynucleotidyl transferase-mediated, dUTP-biotin nick-end labeling (TUNEL) method and an immunohistochemical technique. Primary antibodies used in immunohistochemistry were against pentosidine, ubiquitin and caspase 12. Histological localization of these substances in oocytes was observed by light microscopy, and labeling indices of these cells were evaluated by regression analysis. Positive signals for pentosidine, ubiquitin, caspase 12, and TUNEL were detectable in oocytes of the primordial, primary and their atretic follicles. Regression analysis revealed an age-related increase in the labeling indices for pentosidine, ubiquitin, caspase 12, and TUNEL. These results suggest that pentosidine accumulation in human oocytes is related to apoptosis and increases with age. Further studies will be necessary to clarify the involvement of pentosidine accumulation, proteasome inhibition, and endoplasmic reticulum stress in age-related apoptosis of oocytes in human ovaries. PMID:18787640

  1. Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans.

    PubMed

    Wertheimer, Anne M; Bennett, Michael S; Park, Byung; Uhrlaub, Jennifer L; Martinez, Carmine; Pulko, Vesna; Currier, Noreen L; Nikolich-Žugich, Dragana; Kaye, Jeffrey; Nikolich-Žugich, Janko

    2014-03-01

    The impact of intrinsic aging upon human peripheral blood T cell subsets remains incompletely quantified and understood. This impact must be distinguished from the influence of latent persistent microorganisms, particularly CMV, which has been associated with age-related changes in the T cell pool. In a cross-sectional cohort of 152 CMV-negative individuals, aged 21-101 y, we found that aging correlated strictly to an absolute loss of naive CD8, but not CD4, T cells but, contrary to many reports, did not lead to an increase in memory T cell numbers. The loss of naive CD8 T cells was not altered by CMV in 239 subjects (range 21-96 y), but the decline in CD4(+) naive cells showed significance in CMV(+) individuals. These individuals also exhibited an absolute increase in the effector/effector memory CD4(+) and CD8(+) cells with age. That increase was seen mainly, if not exclusively, in older subjects with elevated anti-CMV Ab titers, suggesting that efficacy of viral control over time may determine the magnitude of CMV impact upon T cell memory, and perhaps upon immune defense. These findings provide important new insights into the age-related changes in the peripheral blood pool of older adults, demonstrating that aging and CMV exert both distinct and joint influence upon blood T cell homeostasis in humans. PMID:24501199

  2. Virtual navigation in humans: the impact of age, sex, and hormones on place learning.

    PubMed

    Driscoll, Ira; Hamilton, Derek A; Yeo, Ronald A; Brooks, William M; Sutherland, Robert J

    2005-03-01

    Certain cognitive processes, including spatial ability, decline with normal aging. Spatial ability is also a cognitive domain with robust sex differences typically favoring males. However, tests of spatial ability do not seem to measure a homogeneous class of processes. For many, mentally matching rotated three-dimensional images is the gold standard for measuring spatial cognition in humans, while the Morris water task (MWT) is a preferred method in the domain of nonhuman animal research. The MWT is sensitive to hippocampal damage, a structure critical for normal learning and memory and often implicated in age-related cognitive decline. A computerized (virtual) version of the MWT (VMWT) appears to require and engage human hippocampal circuitry, and has proven useful in studying sex differences and testing spatial learning theories. In Experiment 1, we tested participants (20-90 years of age) in the VMWT and compared their performance to that on the Vandenberg Mental Rotation Test. We report an age-related deficit in performance on both tasks. In Experiment 2, we tested young (age 20-39) and elderly (age >60) participants in the VMWT and correlated their performance to the circulating levels of testosterone and cortisol. Our findings indicate that the persistence of male spatial advantage may be related to circulating testosterone, but not cortisol levels, and independent of generalized age-related cognitive decline.

  3. Erythrocyte membrane transporters during human ageing: modulatory role of tea catechins.

    PubMed

    Pandey, Kanti Bhooshan; Jha, Rashmi; Rizvi, Syed Ibrahim

    2013-02-01

    Ageing is associated with many physiological and cellular changes, many of which are due to alterations in the plasma membrane. The functions of membrane transporter proteins are crucial for the maintenance of ionic homeostasis between the extra- and intracellular environments. The aim of the present study was to determine the status of erythrocyte membrane transporters, specifically Ca(2+) -ATPases, Na(+) /K(+) -ATPases and the Na(+) /H(+) exchanger (NHE), during ageing in humans. Furthermore, because tea catechins have been reported to possess strong anti-oxidant potential, the study was extended to evaluate the effect of (-)-epicatechin (EC), (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin (EGC) and (-)-epigallocatechin-3-gallate (EGCG) on these transporters as a function of human age. The study was performed on 97 normal healthy subjects (62 men, 35 women; 16-80 years old). To investigate the effects of tea catechins, subjects were divided into three groups: young (<40 years old; n = 34); middle-aged (40-60 years old; n = 32); and old (>60 years old; n = 31). Erythrocyte ghosts/cell suspension from each group were incubated with ECG, EGCG, EGC and EC (10 μmol/L) for 30 min at 37°C prior to assay. Ageing significantly increased NHE activity and decreased Ca(2+) -ATPase activity. There were no significant changes in Na(+) /K(+) -ATPase activity during the ageing process. (-)-Epigallocatechin-3-gallate, EGC, ECG and EC effectively mitigated the changes in membrane transporter activity in erythrocytes from all age groups; however, the effect was more pronounced in the old age group. We hypothesize that impairment in -bound transporters may be one of the possible mechanisms underlying the pathological events during ageing. A higher intake of catechin-rich food may provide some protection against age-dependent diseases.

  4. Age-related changes in midbrain dopaminergic regulation of the human reward system

    PubMed Central

    Dreher, Jean-Claude; Meyer-Lindenberg, Andreas; Kohn, Philip; Berman, Karen Faith

    2008-01-01

    The dopamine system, which plays a crucial role in reward processing, is particularly vulnerable to aging. Significant losses over a normal lifespan have been reported for dopamine receptors and transporters, but very little is known about the neurofunctional consequences of this age-related dopaminergic decline. In animals, a substantial body of data indicates that dopamine activity in the midbrain is tightly associated with reward processing. In humans, although indirect evidence from pharmacological and clinical studies also supports such an association, there has been no direct demonstration of a link between midbrain dopamine and reward-related neural response. Moreover, there are no in vivo data for alterations in this relationship in older humans. Here, by using 6-[18F]FluoroDOPA (FDOPA) positron emission tomography (PET) and event-related 3T functional magnetic resonance imaging (fMRI) in the same subjects, we directly demonstrate a link between midbrain dopamine synthesis and reward-related prefrontal activity in humans, show that healthy aging induces functional alterations in the reward system, and identify an age-related change in the direction of the relationship (from a positive to a negative correlation) between midbrain dopamine synthesis and prefrontal activity. These results indicate an age-dependent dopaminergic tuning mechanism for cortical reward processing and provide system-level information about alteration of a key neural circuit in healthy aging. Taken together, our findings provide an important characterization of the interactions between midbrain dopamine function and the reward system in healthy young humans and older subjects, and identify the changes in this regulatory circuit that accompany aging. PMID:18794529

  5. Lens of Eye Dosimetry

    SciTech Connect

    Mallett, Michael Wesley

    2015-03-23

    An analysis of LANL occupational dose measurements was made with respect to lens of eye dose (LOE), in particular, for plutonium workers. Table 1 shows the reported LOE as a ratio of the “deep” (photon only) and “deep+neutron” dose for routine monitored workers at LANL for the past ten years. The data compares the mean and range of these values for plutonium workers* and non-routine plutonium workers. All doses were reported based on measurements with the LANL Model 8823 TLD.

  6. Physics of electrostatic lens

    NASA Astrophysics Data System (ADS)

    1981-09-01

    The purpose of this program was to study the physics of the ion-energy boosting electrostatic lens for collective ion acceleration in the Luce diode. Extensive work was done in preparation for experiments on the PI Pulserad 1150. Analytic work was done on the orbit of protons in a mass spectrometer and a copper stack for nuclear activation analysis of proton energy spectrum has been designed. Unfortunately, a parallel program which would provide the Luce diode for the collective ion acceleration experiment never materialized. As a result no experiments were actually performed on the Pulserad 1150.

  7. The 2014 IODC lens design problem: the Cinderella lens

    NASA Astrophysics Data System (ADS)

    Juergens, Richard C.

    2014-12-01

    The lens design problem for the 2014 IODC is to design a 100 mm focal length lens in which all the components of the lens can be manufactured from ten Schott N-BK7 lens blanks 100 mm in diameter x 30 mm thick. The lens is used monochromatically at 587.56 nm. The goal of the problem is to maximize the product of the entrance pupil diameter and the semi-field of view while holding the RMS wavefront error to <= 0.070 wave within the field of view. There were 45 entries from 13 different countries. Four different commercial lens design programs were used, along with six custom, in-house programs. The number of lens elements in the entries ranged from 10 to 52. The winning entry from Jon Ehrmann had 25 lens elements, and had an entrance pupil diameter of 33.9 mm and a semi-field of view of 62.5° for a merit function product of 2,119.

  8. The Wnt/beta-catenin pathway is activated during advanced arterial aging in humans.

    PubMed

    Marchand, Alexandre; Atassi, Fabrice; Gaaya, Amira; Leprince, Pascal; Le Feuvre, Claude; Soubrier, Florent; Lompré, Anne-Marie; Nadaud, Sophie

    2011-04-01

    Aging is the main risk factor for cardiovascular diseases, but the associated molecular mechanisms are poorly understood. The Wnt signaling pathway was shown to be induced during aging in muscle and in the skin, but the regulation and role of Wnt signaling in the aged vessel have not yet been addressed. While screening for age-related changes in gene expression in the intima/media of human mammary arteries, we observed that the expression of frizzled 4 (Fzd4), a Wnt receptor, and of several targets of the Wnt/β-catenin/TCF signaling pathway [Wnt-inducible secreted protein 1 (WISP1), versican, osteopontin (SPP1), insulin-like growth factor binding protein 2 (IGFBP-2), and p21] were modified with age, suggesting an activation of the Wnt/β-catenin pathway. In contrast, we did not observe any regulation of forkhead transcription factor (FoxO) target genes. Beta-catenin-activating phosphorylation at position Ser675 was increased in aging mammary arteries, confirming the activation of this pathway. We confirmed in vitro that Wnt3a or Wnt1 treatment of human vascular smooth muscle cells (VSMCs) induced β-catenin phosphorylation at Ser675 and WISP1, SPP1, and IGFBP-2 expression. In vitro, Wnt treatment induced proliferation and cyclin D1 expression in VSMC from young (6 weeks old) rats but not in cells from older rats (8 months old), even though low-density lipoprotein receptor-related protein 6 and β-catenin phosphorylation, and β-catenin nuclear translocation demonstrated β-catenin activation in both cell types. Beta-catenin silencing demonstrated that Wnt induction of cyclin D1 expression is β-catenin dependent. Altogether, our data show that the Wnt/β-catenin/TCF pathway is activated in aging human mammary artery cells, but fails to induce the proliferation of aging vascular cells. PMID:21108734

  9. Human aneuploidy: mechanisms and new insights into an age-old problem

    PubMed Central

    Nagaoka, So I.; Hassold, Terry J.; Hunt, Patricia A.

    2012-01-01

    Trisomic and monosomic (aneuploid) embryos account for at least 10% of human pregnancies and, for women nearing the end of their reproductive lifespan, the incidence may exceed 50%. The errors that lead to aneuploidy almost always occur in the oocyte but, despite intensive investigation, the underlying molecular basis has remained elusive. Recent studies of humans and model organisms have shed new light on the complexity of meiotic defects, providing evidence that the age-related increase in errors in the human female is not attributable to a single factor but to an interplay between unique features of oogenesis and a host of endogenous and exogenous factors. PMID:22705668

  10. Coordinated Expression of Phosphoinositide Metabolic Genes during Development and Aging of Human Dorsolateral Prefrontal Cortex

    PubMed Central

    Rapoport, Stanley I.; Primiani, Christopher T.; Chen, Chuck T.; Ahn, Kwangmi; Ryan, Veronica H.

    2015-01-01

    Background Phosphoinositides, lipid-signaling molecules, participate in diverse brain processes within a wide metabolic cascade. Hypothesis Gene transcriptional networks coordinately regulate the phosphoinositide cascade during human brain Development and Aging. Methods We used the public BrainCloud database for human dorsolateral prefrontal cortex to examine age-related expression levels of 49 phosphoinositide metabolic genes during Development (0 to 20+ years) and Aging (21+ years). Results We identified three groups of partially overlapping genes in each of the two intervals, with similar intergroup correlations despite marked phenotypic differences between Aging and Development. In each interval, ITPKB, PLCD1, PIK3R3, ISYNA1, IMPA2, INPPL1, PI4KB, and AKT1 are in Group 1, PIK3CB, PTEN, PIK3CA, and IMPA1 in Group 2, and SACM1L, PI3KR4, INPP5A, SYNJ1, and PLCB1 in Group 3. Ten of the genes change expression nonlinearly during Development, suggesting involvement in rapidly changing neuronal, glial and myelination events. Correlated transcription for some gene pairs likely is facilitated by colocalization on the same chromosome band. Conclusions Stable coordinated gene transcriptional networks regulate brain phosphoinositide metabolic pathways during human Development and Aging. PMID:26168237

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

    PubMed Central

    Sykiotis, Gerasimos P.; Bohmann, Dirk

    2010-01-01

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

  12. Comparison of biaxial mechanical properties of coronary sinus tissues from porcine, ovine and aged human species.

    PubMed

    Pham, Thuy; Sun, Wei

    2012-02-01

    Due to its proximity to the mitral valve, the coronary sinus (CS) vessel serves as a conduit for the deployment and implantation of the percutaneous transvenous mitral annuloplasty (PTMA) devices that can potentially reduce the mitral regurgitation. Because CS vessel is a venous tissue and seldom diseased, its mechanical properties have not been well studied. In this study, we performed a multi-axial mechanical test and histological analysis to characterize the mechanical and structural properties of the aged human, porcine and ovine CS tissues. The results showed that the aged human CS tissues exhibited much stiffer and highly anisotropic behaviors compared to the porcine and ovine. Both of the porcine and ovine CS vessel walls were thicker and mainly composed of striated muscle fibers (SMF), whereas the thinner aged human CS had higher collagen, less SMF, and more fragmented elastin fibers, which are possibly due to aging effects. We also observed that the anatomical features of porcine CS vessel might be not suitable for PTMA deployment. These differences between animal and human models raise questions for the validity of using animal models to investigate the biomechanics involved in the PTMA intervention. Therefore, caution must be taken in future studies of PTMA stents using animal models.

  13. Three-dimensional and stereological characterization of the human substantia nigra during aging.

    PubMed

    Di Lorenzo Alho, Ana Tereza; Suemoto, Claudia Kimie; Polichiso, Lívia; Tampellini, Edilaine; de Oliveira, Kátia Cristina; Molina, Mariana; Santos, Glaucia Aparecida Bento; Nascimento, Camila; Leite, Renata Elaine Paraizo; de Lucena Ferreti-Rebustini, Renata Eloah; da Silva, Alexandre Valotta; Nitrini, Ricardo; Pasqualucci, Carlos Augusto; Jacob-Filho, Wilson; Heinsen, Helmut; Grinberg, Lea Tenenholz

    2016-09-01

    The human brain undergoes non-uniform changes during aging. The substantia nigra (SN), the source of major dopaminergic pathways in the brain, is particularly vulnerable to changes in the progression of several age-related neurodegenerative diseases. To establish normative data for high-resolution imaging, and to further clinical and anatomical studies we analyzed SNs from 15 subjects aged 50-91 cognitively normal human subjects without signs of parkinsonism. Complete brains or brainstems with substantia nigra were formalin-fixed, celloidin-mounted, serially cut and Nissl-stained. The shapes of all SNs investigated were reconstructed using fast, high-resolution computer-assisted 3D reconstruction software. We found a negative correlation between age and SN volume (p = 0.04, rho = -0.53), with great variability in neuronal numbers and density across participants. The 3D reconstructions revealed SN inter- and intra-individual variability. Furthermore, we observed that human SN is a neuronal reticulum, rather than a group of isolated neuronal islands. Caution is required when using SN volume as a surrogate for SN status in individual subjects. The use of multimodal sequences including those for fiber tracts may enhance the value of imaging as a diagnostic tool to assess SN in vivo. Further studies with a larger sample size are needed for understanding the structure-function interaction of human SN.

  14. Individual Differences in Spatial Pattern Separation Performance Associated with Healthy Aging in Humans

    ERIC Educational Resources Information Center

    Stark, Shauna M.; Yassa, Michael A.; Stark, Craig E. L.

    2010-01-01

    Rodent studies have suggested that "pattern separation," the ability to distinguish among similar experiences, is diminished in a subset of aged rats. We extended these findings to the human using a task designed to assess spatial pattern separation behavior (determining at time of test whether pairs of pictures shown during the study were in the…

  15. Rural origin, age, and endoparasite fecal prevalence in dogs surrendered to the Regina Humane Society, 2013

    PubMed Central

    Schurer, Janna M.; Hamblin, Brie; Davenport, Laura; Wagner, Brent; Jenkins, Emily J.

    2014-01-01

    We report the results of fecal parasite surveillance in dogs surrendered to the Regina Humane Society, Saskatchewan, Canada, between May and November 2013. Overall, 23% of 231 dogs were infected with at least 1 intestinal parasite. Endoparasite infection was positively associated with rural origin (P = 0.002) and age (< 12 months; P < 0.001). PMID:25477549

  16. Not so Big Communities: A Promising Future for Human Beings of All Ages

    ERIC Educational Resources Information Center

    Susanka, Sarah

    2011-01-01

    In many American communities today, the methods of construction, as well as the almost exclusive orientation to the convenience of the automobile, limit the functioning and independence of the aging population, and offer little opportunity for human interaction. Sarah Susanka's "Not So Big" series of books points toward a new way of building…

  17. Nutrition and the biology of human ageing: Proceedings of the ninth nestle international nutrition symposium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This 9th Nestle Nutrition Symposium on “Nutrition and the Biology of Human Ageing” is presented at a time of unprecedented demographic change worldwide. The UN population division forecasts that the number of people living over age 65 will rise to almost 1 billion (12% percent of the world’s populat...