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Sample records for melanogaster reduces age-related

  1. Age-related Decline of Abiotic Stress Tolerance in Young Drosophila melanogaster Adults.

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    Colinet, Hervé; Chertemps, Thomas; Boulogne, Isabelle; Siaussat, David

    2016-12-01

    Stress tolerance generally declines with age as a result of functional senescence. Age-dependent alteration of stress tolerance can also occur in early adult life. In Drosophila melanogaster, evidence of such a decline in young adults has only been reported for thermotolerance. It is not known whether early adult life entails a general stress tolerance reduction and whether the response is peculiar to thermal traits. The present work was designed to investigate whether newly eclosed D melanogaster adults present a high tolerance to a range of biotic and abiotic insults. We found that tolerance to most of the abiotic stressors tested (desiccation, paraquat, hydrogen peroxide, deltamethrin, and malathion) was high in newly eclosed adults before dramatically declining over the next days of adult life. No clear age-related pattern was found for resistance to biotic stress (septic or fungal infection) and starvation. These results suggest that newly eclosed adults present a culminating level of tolerance to extrinsic stress which is likely unrelated to immune process. We argue that stress tolerance variation at very young age is likely a residual attribute from the previous life stage (ontogenetic carryover) or a feature related to the posteclosion development. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Auditory white noise reduces age-related fluctuations in balance.

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    Ross, J M; Will, O J; McGann, Z; Balasubramaniam, R

    2016-09-06

    Fall prevention technologies have the potential to improve the lives of older adults. Because of the multisensory nature of human balance control, sensory therapies, including some involving tactile and auditory noise, are being explored that might reduce increased balance variability due to typical age-related sensory declines. Auditory white noise has previously been shown to reduce postural sway variability in healthy young adults. In the present experiment, we examined this treatment in young adults and typically aging older adults. We measured postural sway of healthy young adults and adults over the age of 65 years during silence and auditory white noise, with and without vision. Our results show reduced postural sway variability in young and older adults with auditory noise, even in the absence of vision. We show that vision and noise can reduce sway variability for both feedback-based and exploratory balance processes. In addition, we show changes with auditory noise in nonlinear patterns of sway in older adults that reflect what is more typical of young adults, and these changes did not interfere with the typical random walk behavior of sway. Our results suggest that auditory noise might be valuable for therapeutic and rehabilitative purposes in older adults with typical age-related balance variability. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Age-Related Reduced Somatosensory Gating Is Associated with Altered Alpha Frequency Desynchronization

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    Cheng, Chia-Hsiung; Chan, Pei-Ying S.; Lin, Yung-Yang

    2015-01-01

    Sensory gating (SG), referring to an attenuated neural response to the second identical stimulus, is considered as preattentive processing in the central nervous system to filter redundant sensory inputs. Insufficient somatosensory SG has been found in the aged adults, particularly in the secondary somatosensory cortex (SII). However, it remains unclear which variables leading to the age-related somatosensory SG decline. There has been evidence showing a relationship between brain oscillations and cortical evoked excitability. Thus, this study used whole-head magnetoencephalography to record responses to paired-pulse electrical stimulation to the left median nerve in healthy young and elderly participants to test whether insufficient stimulus 1- (S1-) induced event-related desynchronization (ERD) contributes to a less-suppressed stimulus 2- (S2-) evoked response. Our analysis revealed that the minimum norm estimates showed age-related reduction of SG in the bilateral SII regions. Spectral power analysis showed that the elderly demonstrated significantly reduced alpha ERD in the contralateral SII (SIIc). Moreover, it was striking to note that lower S1-induced alpha ERD was associated with higher S2-evoked amplitudes in the SIIc among the aged adults. Conclusively, our findings suggest that age-related decline of somatosensory SG is partially attributed to the altered S1-induced oscillatory activity. PMID:26417458

  4. Age-Related Reduced Somatosensory Gating Is Associated with Altered Alpha Frequency Desynchronization

    Directory of Open Access Journals (Sweden)

    Chia-Hsiung Cheng

    2015-01-01

    Full Text Available Sensory gating (SG, referring to an attenuated neural response to the second identical stimulus, is considered as preattentive processing in the central nervous system to filter redundant sensory inputs. Insufficient somatosensory SG has been found in the aged adults, particularly in the secondary somatosensory cortex (SII. However, it remains unclear which variables leading to the age-related somatosensory SG decline. There has been evidence showing a relationship between brain oscillations and cortical evoked excitability. Thus, this study used whole-head magnetoencephalography to record responses to paired-pulse electrical stimulation to the left median nerve in healthy young and elderly participants to test whether insufficient stimulus 1- (S1- induced event-related desynchronization (ERD contributes to a less-suppressed stimulus 2- (S2- evoked response. Our analysis revealed that the minimum norm estimates showed age-related reduction of SG in the bilateral SII regions. Spectral power analysis showed that the elderly demonstrated significantly reduced alpha ERD in the contralateral SII (SIIc. Moreover, it was striking to note that lower S1-induced alpha ERD was associated with higher S2-evoked amplitudes in the SIIc among the aged adults. Conclusively, our findings suggest that age-related decline of somatosensory SG is partially attributed to the altered S1-induced oscillatory activity.

  5. High Cognitive Reserve is associated with a reduced age-related deficit in spatial conflict resolution.

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    Olga ePuccioni

    2012-12-01

    Full Text Available Several studies support the existence of a specific age-related difficulty in suppressing potentially distracting information. The aim of the present study is to investigate whether spatial conflict resolution is selectively affected by aging. The way aging affects individuals could be modulated by many factors determined by the socieconomic status: we investigated whether factors such as cognitive reserve (CR and years of education may play a compensatory role against age-related deficits in the spatial domain. A spatial Stroop task with no feature repetitions was administered to a sample of 17 non-demented older adults (69-79 years old and 18 younger controls (18-34 years old matched for gender and years of education. The two age groups were also administered with measures of intelligence and CR. The overall spatial Stroop effect did not differ according to age, neither for speed nor for accuracy. The two age groups equally showed sequential effects for congruent trials: reduced response times (RTs if another congruent trial preceded them, and accuracy at ceiling. For incongruent trials, older adults, but not younger controls, were influenced by congruency of trialn-1, since RTs increased with preceding congruent trials. Interestingly, such an age-related modulation negatively correlated with CR. These findings suggest that spatial conflict resolution in aging is predominantly affected by general slowing, rather than by a more specific deficit. However, a high level of CR seems to play a compensatory role for both factors.

  6. High cognitive reserve is associated with a reduced age-related deficit in spatial conflict resolution

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    Puccioni, Olga; Vallesi, Antonino

    2012-01-01

    Several studies support the existence of a specific age-related difficulty in suppressing potentially distracting information. The aim of the present study is to investigate whether spatial conflict resolution is selectively affected by aging. The way aging affects individuals could be modulated by many factors determined by the socieconomic status: we investigated whether factors such as cognitive reserve (CR) and years of education may play a compensatory role against age-related deficits in the spatial domain. A spatial Stroop task with no feature repetitions was administered to a sample of 17 non-demented older adults (69–79 years-old) and 18 younger controls (18–34 years-old) matched for gender and years of education. The two age groups were also administered with measures of intelligence and CR. The overall spatial Stroop effect did not differ according to age, neither for speed nor for accuracy. The two age groups equally showed sequential effects for congruent trials: reduced response times (RTs) if another congruent trial preceded them, and accuracy at ceiling. For incongruent trials, older adults, but not younger controls, were influenced by congruency of trialn−1, since RTs increased with preceding congruent trials. Interestingly, such an age-related modulation negatively correlated with CR. These findings suggest that spatial conflict resolution in aging is predominantly affected by general slowing, rather than by a more specific deficit. However, a high level of CR seems to play a compensatory role for both factors. PMID:23248595

  7. Age-related reduced prefrontal-amygdala structural connectivity is associated with lower trait anxiety

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    Clewett, David; Bachman, Shelby; Mather, Mara

    2014-01-01

    Objective A current neuroanatomical model of anxiety posits that greater structural connectivity between the amygdala and ventral prefrontal cortex (vPFC) facilitates regulatory control over the amygdala and helps reduce anxiety. However, some neuroimaging studies have reported contradictory findings, demonstrating a positive rather than negative association between trait anxiety and amygdala-vPFC white matter integrity. To help reconcile these findings, we tested the regulatory hypothesis of anxiety circuitry using aging as a model of white matter decline in the amygdala-vPFC pathway. Methods We used probabilistic tractography to trace connections between the amygdala and vPFC in 21 younger, 18 middle-aged, and 15 healthy older adults. The resulting tract estimates were used to extract three indices of white-matter integrity: fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD). The relationship between these amygdala-vPFC structural connectivity measures and age and State-Trait Anxiety Inventory (STAI) scores were assessed. Results The tractography results revealed age-related decline in the FA (p = .005) and radial diffusivity (p = .002) of the amygdala-vPFC pathway. Contrary to the regulatory hypothesis, we found a positive rather than negative association between trait anxiety and right amygdala-vPFC FA (p = .01). Conclusion These findings argue against the notion that greater amygdala-vPFC structural integrity facilitates better anxiety outcomes in healthy adults. Instead, our results suggest that white matter degeneration in this network relates to lower anxiety in older adults. PMID:24635708

  8. Intranasal oxytocin does not reduce age-related difficulties in social cognition.

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    Grainger, Sarah A; Henry, Julie D; Steinvik, Henriette R; Vanman, Eric J; Rendell, Peter G; Labuschagne, Izelle

    2018-03-01

    Oxytocin is a neuropeptide that plays a key role in social processing and there are several studies suggesting that intranasally administered oxytocin may enhance social cognitive abilities and visual attention in healthy and clinical groups. However, there are very few studies to date that have investigated the potential benefits of intranasal oxytocin (iOT) on older adults' social cognitive abilities. This is a surprising omission, because relative to their younger counterparts, older adults also exhibit a range of social cognitive difficulties and also show differences in the way they visually attend to social information. Therefore, we tested the effect of iOT (24 IU) versus a placebo spray on 59 older and 61 younger adults' social cognitive abilities and visual attention using a double-blind placebo-controlled within-groups design. While iOT provided no overall age-related benefit on social cognitive abilities, the key finding to emerge was that iOT improved ToM ability in both age-groups when the task had minimal contextual information, but not when the task had enriched contextual information. Interestingly, iOT had gender specific effects during a ToM task with minimal context. For males in both age-groups, iOT reduced gazing to the social aspects of the scenes (i.e., faces & bodies), and for females, iOT eliminated age differences in gaze patterns that were observed in the placebo condition. These effects on eye-gaze were not observed in a very similar ToM task that included more enriched contextual information. Overall, these findings highlight the interactive nature of iOT with task related factors (e.g., context), and are discussed in relation to the social salience hypothesis of oxytocin. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Age-related IQ decline is reduced markedly after adjustment for the Flynn effect.

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    Dickinson, Mercedes D; Hiscock, Merrill

    2010-10-01

    Twenty-year-olds outperform 70-year-olds by as much as 2.3 standard deviations (35 IQ points) on subtests of the Wechsler Adult Intelligence Scale (WAIS). We show that most of the difference can be attributed to an intergenerational rise in IQ known as the Flynn effect. Normative data from different versions of the WAIS enabled us to estimate the degree to which the Flynn effect, rather than age-related decline, contributes to differences between 20- and 70-year-olds. The Flynn effect accounted for 38-67% of the apparent age-related decline on 6 of the 11 subtests. On the other 5 subtests, all of which are categorized as verbal, the Flynn effect was larger than the age-group difference. For these verbal subtests, the Flynn effect masked a modest increase in ability as individuals grow older. Overall, the Flynn effect accounted for at least 85% of the disparity between 20- and 70-year-olds.

  10. Deficiency of circadian protein CLOCK reduces lifespan and increases age-related cataract development in mice

    OpenAIRE

    Dubrovsky, Yuliya V.; Samsa, William E.; Kondratov, Roman V.

    2010-01-01

    Circadian clock is implicated in the regulation of aging. The transcription factor CLOCK, a core component of the circadian system, operates in complex with another circadian clock protein BMAL1. Recently it was demonstrated that BMAL1 deficiency results in premature aging in mice. Here we investigate the aging of mice deficient for CLOCK protein. Deficiency of the CLOCK protein significantly affects longevity: the average lifespan of Clock−/− mice is reduced by 15% compared with wild type mi...

  11. Video games as a means to reduce age-related cognitive decline: attitudes, compliance, and effectiveness.

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    Boot, Walter R; Champion, Michael; Blakely, Daniel P; Wright, Timothy; Souders, Dustin J; Charness, Neil

    2013-01-01

    Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a "brain fitness" game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants' ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why.

  12. Video Games as a Means to Reduce Age-related Cognitive Decline: Attitudes, Compliance, and Effectiveness

    Directory of Open Access Journals (Sweden)

    Walter R. Boot

    2013-02-01

    Full Text Available Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a brain fitness game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game induced the lowest intervention compliance. We explain this low compliance by participants’ ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why.

  13. Oral Doxycycline Reduces the Total Number of Intraocular Bevacizumab Injections Needed to Control Neovascular Age-related Macular Degeneration.

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    Mirshahi, Ahmad; Azimi, Pourya; Abdolahi, Ali; Mirshahi, Romina; Abdollahian, Mahnaz

    2017-01-01

    Tetracyclines, especially doxycycline, play a role in the regulation of inflammation, immunomodulation, cell proliferation, and angiogenesis. Treatment of corneal angiogenesis or choroidal neovascularization with tetracyclines has been shown to be effective in animal models. The aim of this study was to evaluate the efficacy of oral doxycycline in reducing the total number of intraocular injections needed for controlling neovascular age-related macular degeneration in human patients. In this interventional case series, 28 random consecutive patients with neovascular age-related macular degeneration from Farabi Eye Hospital, Tehran, Iran were treated for 4 months with 200 mg doxycycline once a day after the first intravitreal bevacizumab injection in addition to standard therapy in agreement with as-needed regimen. After 12 months of follow-up, total number of injections, foveal thickness and visual acuity were compared to those at baseline and of similar studies. Similar to standard treatment, co-treatment with doxycycline was able to control active disease (intraretinal or subretinal fluid or leakage, new-onset of macular hemorrhage, and reduction of visual acuity more than 5 letters based on Early Treatment Diabetic Retinopathy Study [ETDRS] charts) yet with fewer injections (for current study and standard treatment, respectively 3.14 vs. 5.92, P 0.05). If confirmed in larger studies, the findings of this interventional case series could provide a strategy to control neovascular age-related macular degeneration with fewer intraocular bevacizumab injections by co-administering a well-known oral agent-doxycycline.

  14. Photobiomodulation reduces drusen volume and improves visual acuity and contrast sensitivity in dry age-related macular degeneration.

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    Merry, Graham F; Munk, Marion R; Dotson, Robert S; Walker, Michael G; Devenyi, Robert G

    2017-06-01

    To evaluate the efficacy of photobiomodulation (PBM) treatment for patients with dry age-related macular degeneration (AMD). Assessments on 42 eyes with dry AMD (age related eye disease study (AREDS) 2-4) were conducted. Multiwavelength light emitting diode (LED) light comprising of yellow (590 nm), red (670 nm) and near-infrared (790 nm) bandwidths was applied to subjects' eyes for a treatment course of 3 weeks. Outcome measures were changes in best-corrected visual acuity (BCVA), contrast sensitivity (CS), drusen volume and central drusen thickness. Significant improvement in mean BCVA of 5.90 letters (p < 0.001) was seen on completion of the 3-week treatment and 5.14 letters (p < 0.001) after 3 months. Contrast sensitivity improved significantly (log unit improvement of 0.11 (p = 0.02) at 3 weeks and 3 months (log unit improvement of 0.16 (p = 0.02) at three cycles per degree. Drusen volume decreased by 0.024 mm 3 (p < 0.001) and central drusen thickness was significantly reduced by a mean of 3.78 μm (p < 0.001), while overall central retinal thickness and retinal volume remained stable. This is the first study demonstrating improvements in functional and anatomical outcomes in dry AMD subjects with PBM therapy. These findings corroborate an earlier pilot study that looked at functional outcome measures. The addition of anatomical evidence contributes to the basis for further development of a non-invasive PBM treatment for dry AMD. © 2016 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.

  15. Metabolic and functional phenotypic profiling of Drosophila melanogaster reveals reduced sex differentiation under stressful environmental conditions

    DEFF Research Database (Denmark)

    Ørsted, Michael; Malmendal, Anders; Muñoz, Joaquin

    2017-01-01

    Strong sexual dimorphism is commonly observed across species and e.g. trade-offs between reproduction and maintenance are thought to explain this dimorphism. Here we test how the metabolic and functional phenotypic responses to varying types of environmental stress differ in male and female...... rearing regimes were investigated using NMR metabolomics and assessed for body mass and viability. Our results showed that environmental stress leads to reduced sexual dimorphism in both metabolic composition and body mass compared to the level of dimorphism observed at benign conditions. This reduced...... Drosophila melanogaster (Diptera: Drosophilidae), and how this impacts the magnitude of sexual dimorphism. Experimental stressors that we exposed flies to during development were heat stress, poor nutrition, high acidity, high levels of ammonia and ethanol. Emerged male and female flies from the different...

  16. Resveratrol prevents age-related memory and mood dysfunction with increased hippocampal neurogenesis and microvasculature, and reduced glial activation.

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    Kodali, Maheedhar; Parihar, Vipan K; Hattiangady, Bharathi; Mishra, Vikas; Shuai, Bing; Shetty, Ashok K

    2015-01-28

    Greatly waned neurogenesis, diminished microvasculature, astrocyte hypertrophy and activated microglia are among the most conspicuous structural changes in the aged hippocampus. Because these alterations can contribute to age-related memory and mood impairments, strategies efficacious for mitigating these changes may preserve cognitive and mood function in old age. Resveratrol, a phytoalexin found in the skin of red grapes having angiogenic and antiinflammatory properties, appears ideal for easing these age-related changes. Hence, we examined the efficacy of resveratrol for counteracting age-related memory and mood impairments and the associated detrimental changes in the hippocampus. Two groups of male F344 rats in late middle-age having similar learning and memory abilities were chosen and treated with resveratrol or vehicle for four weeks. Analyses at ~25 months of age uncovered improved learning, memory and mood function in resveratrol-treated animals but impairments in vehicle-treated animals. Resveratrol-treated animals also displayed increased net neurogenesis and microvasculature, and diminished astrocyte hypertrophy and microglial activation in the hippocampus. These results provide novel evidence that resveratrol treatment in late middle age is efficacious for improving memory and mood function in old age. Modulation of the hippocampus plasticity and suppression of chronic low-level inflammation appear to underlie the functional benefits mediated by resveratrol.

  17. Embryo-larval exposure to atrazine reduces viability and alters oxidative stress parameters in Drosophila melanogaster.

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    Figueira, Fernanda Hernandes; Aguiar, Lais Mattos de; Rosa, Carlos Eduardo da

    2017-01-01

    The herbicide atrazine has been used worldwide with subsequent residual contamination of water and food, which may cause adverse effects on non-target organisms. Animal exposure to this herbicide may affect development, reproduction and energy metabolism. Here, the effects of atrazine regarding survival and redox metabolism were assessed in the fruit fly D. melanogaster exposed during embryonic and larval development. The embryos (newly fertilized eggs) were exposed to different atrazine concentrations (10μM and 100μM) in the diet until the adult fly emerged. Pupation and emergence rates, developmental time and sex ratio were determined as well as oxidative stress parameters and gene expression of the antioxidant defence system were evaluated in newly emerged male and female flies. Atrazine exposure reduced pupation and emergence rates in fruit flies without alterations to developmental time and sex ratio. Different redox imbalance patterns were observed between males and females exposed to atrazine. Atrazine caused an increase in oxidative damage, reactive oxygen species generation and antioxidant capacity and decreased thiol-containing molecules. Further, atrazine exposure altered the mRNA expression of antioxidant genes (keap1, sod, sod2, cat, irc, gss, gclm, gclc, trxt, trxr-1 and trxr-2). Reductions in fruit fly larval and pupal viability observed here are likely consequences of the oxidative stress induced by atrazine exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Probiotic Lactobacillus rhamnosus Reduces Organophosphate Pesticide Absorption and Toxicity to Drosophila melanogaster.

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    Trinder, Mark; McDowell, Tim W; Daisley, Brendan A; Ali, Sohrab N; Leong, Hon S; Sumarah, Mark W; Reid, Gregor

    2016-10-15

    Organophosphate pesticides used in agriculture can pose health risks to humans and wildlife. We hypothesized that dietary supplementation with Lactobacillus, a genus of commensal bacteria, would reduce absorption and toxicity of consumed organophosphate pesticides (parathion and chlorpyrifos [CP]). Several Lactobacillus species were screened for toleration of 100 ppm of CP or parathion in MRS broth based on 24-h growth curves. Certain Lactobacillus strains were unable to reach stationary-phase culture maxima and displayed an abnormal culture morphology in response to pesticide. Further characterization of commonly used, pesticide-tolerant and pesticide-susceptible, probiotic Lactobacillus rhamnosus strain GG (LGG) and L. rhamnosus strain GR-1 (LGR-1), respectively, revealed that both strains could significantly sequester organophosphate pesticides from solution after 24-h coincubations. This effect was independent of metabolic activity, as L. rhamnosus GG did not hydrolyze CP and no difference in organophosphate sequestration was observed between live and heat-killed strains. Furthermore, LGR-1 and LGG reduced the absorption of 100 μM parathion or CP in a Caco-2 Transwell model of the small intestine epithelium. To determine the effect of sequestration on acute toxicity, newly eclosed Drosophila melanogaster flies were exposed to food containing 10 μM CP with or without supplementation with live LGG. Supplementation with LGG simultaneously, but not with administration of CP 3 days prior (prophylactically), mitigated CP-induced mortality. In summary, the results suggest that L. rhamnosus may be useful for reducing toxic organophosphate pesticide exposure via passive binding. These findings could be transferable to clinical and livestock applications due to affordability and practical ability to supplement products with food-grade bacteria. The consequences of environmental pesticide pollution due to widespread usage in agriculture and soil leaching are becoming a

  19. Reduced learning ability as a consequence of evolutionary adaptation to nutritional stress in Drosophila melanogaster

    OpenAIRE

    Kolss, M.; Kawecki, T. J.

    2008-01-01

    Abstract. 1. Dietary conditions affect cognitive abilities of many species, but it is unclear to what extent this physiological effect translates into an evolutionary relationship.2. A reduction of competitive ability under nutritional stress has been reported as a correlated response to selection for learning ability in Drosophila melanogaster. Here we test whether the reverse holds as well, i.e. whether an evolutionary adaptation to poor food conditions leads to a decrease in learning capac...

  20. Reduced Reproductive Success for a Conditioning Mutant in Experimental Populations of DROSOPHILA MELANOGASTER

    OpenAIRE

    Gailey, Donald A.; Hall, Jeffrey C.; Siegel, Richard W.

    1985-01-01

    Male Drosophila melanogaster that have courted newly-emerged males can modify their subsequent courtship behavior to avoid further courtship with immature males for up to 6 hr (previously reported). Here, it was hypothesized that such an experience-dependent modification would afford a mating advantage to normal males over males that carried a mutation that affects learning and memory. Coisogenic lines were constructed which varied at the dunce gene ( dnc+ and dncM14 alleles) in order to test...

  1. A Proinflammatory Function of Toll-Like Receptor 2 in the Retinal Pigment Epithelium as a Novel Target for Reducing Choroidal Neovascularization in Age-Related Macular Degeneration.

    Science.gov (United States)

    Feng, Lili; Ju, Meihua; Lee, Kei Ying V; Mackey, Ashley; Evangelista, Mariasilvia; Iwata, Daiju; Adamson, Peter; Lashkari, Kameran; Foxton, Richard; Shima, David; Ng, Yin Shan

    2017-10-01

    Current treatments for choroidal neovascularization, a major cause of blindness for patients with age-related macular degeneration, treat symptoms but not the underlying causes of the disease. Inflammation has been strongly implicated in the pathogenesis of choroidal neovascularization. We examined the inflammatory role of Toll-like receptor 2 (TLR2) in age-related macular degeneration. TLR2 was robustly expressed by the retinal pigment epithelium in mouse and human eyes, both normal and with macular degeneration/choroidal neovascularization. Nuclear localization of NF-κB, a major downstream target of TLR2 signaling, was detected in the retinal pigment epithelium of human eyes, particularly in eyes with advanced stages of age-related macular degeneration. TLR2 antagonism effectively suppressed initiation and growth of spontaneous choroidal neovascularization in a mouse model, and the combination of anti-TLR2 and antivascular endothelial growth factor receptor 2 yielded an additive therapeutic effect on both area and number of spontaneous choroidal neovascularization lesions. Finally, in primary human fetal retinal pigment epithelium cells, ligand binding to TLR2 induced robust expression of proinflammatory cytokines, and end products of lipid oxidation had a synergistic effect on TLR2 activation. Our data illustrate a functional role for TLR2 in the pathogenesis of choroidal neovascularization, likely by promoting inflammation of the retinal pigment epithelium, and validate TLR2 as a novel therapeutic target for reducing choroidal neovascularization. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. Reduced mitochondrial mass and function add to age-related susceptibility toward diet-induced fatty liver in C57BL/6J mice.

    Science.gov (United States)

    Lohr, Kerstin; Pachl, Fiona; Moghaddas Gholami, Amin; Geillinger, Kerstin E; Daniel, Hannelore; Kuster, Bernhard; Klingenspor, Martin

    2016-10-01

    Nonalcoholic fatty liver disease (NAFLD) is a major health burden in the aging society with an urging medical need for a better understanding of the underlying mechanisms. Mitochondrial fatty acid oxidation and mitochondrial-derived reactive oxygen species (ROS) are considered critical in the development of hepatic steatosis, the hallmark of NAFLD. Our study addressed in C57BL/6J mice the effect of high fat diet feeding and age on liver mitochondria at an early stage of NAFLD development. We therefore analyzed functional characteristics of hepatic mitochondria and associated alterations in the mitochondrial proteome in response to high fat feeding in adolescent, young adult, and middle-aged mice. Susceptibility to diet-induced obesity increased with age. Young adult and middle-aged mice developed fatty liver, but not adolescent mice. Fat accumulation was negatively correlated with an age-related reduction in mitochondrial mass and aggravated by a reduced capacity of fatty acid oxidation in high fat-fed mice. Irrespective of age, high fat diet increased ROS production in hepatic mitochondria associated with a balanced nuclear factor erythroid-derived 2 like 2 (NFE2L2) dependent antioxidative response, most likely triggered by reduced tethering of NFE2L2 to mitochondrial phosphoglycerate mutase 5. Age indirectly influenced mitochondrial function by reducing mitochondrial mass, thus exacerbating diet-induced fat accumulation. Therefore, consideration of age in metabolic studies must be emphasized. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  3. Oxalomalate reduces expression and secretion of vascular endothelial growth factor in the retinal pigment epithelium and inhibits angiogenesis: Implications for age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Sung Hwan Kim

    2016-12-01

    Full Text Available Clinical and experimental observations indicate a critical role for vascular endothelial growth factor (VEGF, secreted by the retinal pigment epithelium (RPE, in pathological angiogenesis and the development of choroidal neovascularization (CNV in age-related macular degeneration (AMD. RPE-mediated VEGF expression, leading to angiogenesis, is a major signaling mechanism underlying ocular neovascular disease. Inhibiting this signaling pathway with a therapeutic molecule is a promising anti-angiogenic strategy to treat this disease with potentially fewer side effects. Oxalomalate (OMA is a competitive inhibitor of NADP+-dependent isocitrate dehydrogenase (IDH, which plays an important role in cellular signaling pathways regulated by reactive oxygen species (ROS. Here, we have investigated the inhibitory effect of OMA on the expression of VEGF, and the associated underlying mechanism of action, using in vitro and in vivo RPE cell models of AMD. We found that OMA reduced the expression and secretion of VEGF in RPE cells, and consequently inhibited CNV formation. This function of OMA was linked to its capacity to activate the pVHL-mediated HIF-1α degradation in these cells, partly via a ROS-dependent ATM signaling axis, through inhibition of IDH enzymes. These findings reveal a novel role for OMA in inhibiting RPE-derived VEGF expression and angiogenesis, and suggest unique therapeutic strategies for treating pathological angiogenesis and AMD development.

  4. Age-Related Vitamin D Deficiency Is Associated with Reduced Macular Ganglion Cell Complex: A Cross-Sectional High-Definition Optical Coherence Tomography Study.

    Science.gov (United States)

    Uro, Mathieu; Beauchet, Olivier; Cherif, Mehdi; Graffe, Alix; Milea, Dan; Annweiler, Cedric

    2015-01-01

    Vitamin D deficiency is associated with smaller volume of optic chiasm in older adults, indicating a possible loss of the visual axons and their cellular bodies. Our objective was to determine whether vitamin D deficiency in older adults is associated with reduced thickness of the ganglion cell complex (GCC) and of the retinal nerve fibre layer (RNFL), as measured with high-definition optical coherence tomography (HD-OCT). Eighty-five French older community-dwellers without open-angle glaucoma and patent age-related macular degeneration (mean, 71.1±4.7 years; 45.9% female) from the GAIT study were separated into 2 groups according to serum 25OHD level (i.e., deficient≤25 nmol/L or sufficient>25 nmol/L). Measurements of GCC and RNFL thickness were performed using HD-OCT. Age, gender, body mass index, number of comorbidities, dementia, functional autonomy, intracranial volume, visual acuity, serum calcium concentration and season of testing were considered as potential confounders. Mean serum 25OHD concentration was 58.4±26.8 nmol/L. Mean logMAR visual acuity was 0.03±0.06. Mean visual field mean deviation was -1.25±2.29 dB. Patients with vitamin D deficiency (n=11) had a reduced mean GCC thickness compared to those without vitamin D deficiency (72.1±7.4 μm versus 77.5±7.5 μm, P=0.028). There was no difference of the mean RNFL thickness in these two groups (P=0.133). After adjustment for potential confounders, vitamin D deficiency was associated with reduced GCC thickness (ß=-5.12, P=0.048) but not RNFL thickness (ß=-9.98, P=0.061). Specifically, vitamin D deficiency correlated with the superior medial GCC area (P=0.017) and superior temporal GCC area (P=0.010). Vitamin D deficiency in older patients is associated with reduced mean GCC thickness, which can represent an early stage of optic nerve damage, prior to RNFL loss.

  5. Age-Related Vitamin D Deficiency Is Associated with Reduced Macular Ganglion Cell Complex: A Cross-Sectional High-Definition Optical Coherence Tomography Study.

    Directory of Open Access Journals (Sweden)

    Mathieu Uro

    Full Text Available Vitamin D deficiency is associated with smaller volume of optic chiasm in older adults, indicating a possible loss of the visual axons and their cellular bodies. Our objective was to determine whether vitamin D deficiency in older adults is associated with reduced thickness of the ganglion cell complex (GCC and of the retinal nerve fibre layer (RNFL, as measured with high-definition optical coherence tomography (HD-OCT.Eighty-five French older community-dwellers without open-angle glaucoma and patent age-related macular degeneration (mean, 71.1±4.7 years; 45.9% female from the GAIT study were separated into 2 groups according to serum 25OHD level (i.e., deficient≤25 nmol/L or sufficient>25 nmol/L. Measurements of GCC and RNFL thickness were performed using HD-OCT. Age, gender, body mass index, number of comorbidities, dementia, functional autonomy, intracranial volume, visual acuity, serum calcium concentration and season of testing were considered as potential confounders.Mean serum 25OHD concentration was 58.4±26.8 nmol/L. Mean logMAR visual acuity was 0.03±0.06. Mean visual field mean deviation was -1.25±2.29 dB. Patients with vitamin D deficiency (n=11 had a reduced mean GCC thickness compared to those without vitamin D deficiency (72.1±7.4 μm versus 77.5±7.5 μm, P=0.028. There was no difference of the mean RNFL thickness in these two groups (P=0.133. After adjustment for potential confounders, vitamin D deficiency was associated with reduced GCC thickness (ß=-5.12, P=0.048 but not RNFL thickness (ß=-9.98, P=0.061. Specifically, vitamin D deficiency correlated with the superior medial GCC area (P=0.017 and superior temporal GCC area (P=0.010.Vitamin D deficiency in older patients is associated with reduced mean GCC thickness, which can represent an early stage of optic nerve damage, prior to RNFL loss.

  6. Effects of reduced natural background radiation on Drosophila melanogaster growth and development as revealed by the FLYINGLOW program.

    Science.gov (United States)

    Morciano, Patrizia; Iorio, Roberto; Iovino, Daniela; Cipressa, Francesca; Esposito, Giuseppe; Porrazzo, Antonella; Satta, Luigi; Alesse, Edoardo; Tabocchini, Maria Antonella; Cenci, Giovanni

    2018-01-01

    Natural background radiation of Earth and cosmic rays played a relevant role during the evolution of living organisms. However, how chronic low doses of radiation can affect biological processes is still unclear. Previous data have indicated that cells grown at the Gran Sasso Underground Laboratory (LNGS, L'Aquila) of National Institute of Nuclear Physics (INFN) of Italy, where the dose rate of cosmic rays and neutrons is significantly reduced with respect to the external environment, elicited an impaired response against endogenous damage as compared to cells grown outside LNGS. This suggests that environmental radiation contributes to the development of defense mechanisms at cellular level. To further understand how environmental radiation affects metabolism of living organisms, we have recently launched the FLYINGLOW program that aims at exploiting Drosophila melanogaster as a model for evaluating the effects of low doses/dose rates of radiation at the organismal level. Here, we will present a comparative data set on lifespan, motility and fertility from different Drosophila strains grown in parallel at LNGS and in a reference laboratory at the University of L'Aquila. Our data suggest the reduced radiation environment can influence Drosophila development and, depending on the genetic background, may affect viability for several generations even when flies are moved back to normal background radiation. As flies are considered a valuable model for human biology, our results might shed some light on understanding the effect of low dose radiation also in humans. © 2017 Wiley Periodicals, Inc.

  7. Diet-derived advanced glycation end products or lipofuscin disrupts proteostasis and reduces life span in Drosophila melanogaster.

    Science.gov (United States)

    Tsakiri, Eleni N; Iliaki, Kalliopi K; Höhn, Annika; Grimm, Stefanie; Papassideri, Issidora S; Grune, Tilman; Trougakos, Ioannis P

    2013-12-01

    Advanced glycation end product (AGE)-modified proteins are formed by the nonenzymatic glycation of free amino groups of proteins and, along with lipofuscin (a highly oxidized aggregate of covalently cross-linked proteins, sugars, and lipids), have been found to accumulate during aging and in several age-related diseases. As the in vivo effects of diet-derived AGEs or lipofuscin remain elusive, we sought to study the impact of oral administration of glucose-, fructose-, or ribose-modified albumin or of artificial lipofuscin in a genetically tractable model organism. We report herein that continuous feeding of young Drosophila flies with culture medium enriched in AGEs or in lipofuscin resulted in reduced locomotor performance and in accelerated rates of AGE-modified proteins and carbonylated proteins accumulation in the somatic tissues and hemolymph of flies, as well as in a significant reduction of flies health span and life span. These phenotypic effects were accompanied by reduced proteasome peptidase activities in both the hemolymph and the somatic tissues of flies and higher levels of oxidative stress; furthermore, oral administration of AGEs or lipofuscin in flies triggered an upregulation of the lysosomal cathepsin B, L activities. Finally, RNAi-mediated cathepsin D knockdown reduced flies longevity and significantly augmented the deleterious effects of AGEs and lipofuscin, indicating that lysosomal cathepsins reduce the toxicity of diet-derived AGEs or lipofuscin. Our in vivo studies demonstrate that chronic ingestion of AGEs or lipofuscin disrupts proteostasis and accelerates the functional decline that occurs with normal aging. © 2013 Elsevier Inc. All rights reserved.

  8. Age-related macular degeneration

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian...

  9. Age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Wanjiku Mathenge

    2014-12-01

    Full Text Available Age-related macular degeneration (AMD is a disease of the retina that usually develops in people aged 60 years and older. It affects about 8.7% of the world’s population and is the leading cause of blindness among people aged 50 and older in industrialised countries.

  10. Age-Related Macular Degeneration.

    Science.gov (United States)

    Mehta, Sonia

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Age-related oral changes.

    LENUS (Irish Health Repository)

    Mckenna, Gerald

    2010-10-01

    Age-related oral changes are seen in the oral hard and soft tissues as well as in bone, the temporomandibular joints and the oral mucosa. As older patients retain their natural teeth for longer, the clinical picture consists of normal physiological age changes in combination with pathological and iatrogenic effects. Clinical Relevance: With an ageing population retaining more of its natural teeth for longer, dental professionals should expect to observe oral age changes more frequently.

  12. Age-related macular degeneration

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

  13. Age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Querques G

    2011-05-01

    Full Text Available Giuseppe Querques¹, Fernando Onofrio Avellis1,2, Lea Querques1,3, Francesco Bandello³, Eric H Souied¹ ¹Service d'Ophtalmologie, Centre Hospitalier Intercommunal Créteil, Université Paris-Est Créteil, Créteil, France; ²Parma Eye Clinic University Hospital, Università degli Studi di Parma, Parma, Italy; ³Department of Ophthalmology, Università Vita-Salute San Raffaele Milano, Milano, Italy Date of preparation: March 3, 2011 Conflict of interest: None declaredClinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD?Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches.Implementation: strategy of administration, safety of intravitreal injectionKeywords: age-related macular degeneration, antivascular endothelial growth factor, choroidal neovascularization, drusen, geographic atrophy

  14. [Presbycusis - Age Related Hearing Loss].

    Science.gov (United States)

    Fischer, N; Weber, B; Riechelmann, H

    2016-07-01

    Presbycusis or age related hearing loss can be defined as a progressive, bilateral and symmetrical sensorineural hearing loss due to age related degeneration of inner ear structures. It can be considered a multifactorial complex disorder with environmental and genetic factors. The molecular, electrophysiological and histological damage at different levels of the inner ear cause a progressive hearing loss, which usually affects the high frequencies of hearing. The resulting poor speech recognition has a negative impact on cognitive, emotional and social function in older adults. Recent investigations revealed an association between hearing impairment and social isolation, anxiety, depression and cognitive decline in elderly. These findings emphasize the importance of diagnosis and treating hearing loss in the elderly population. Hearing aids are the most commonly used devices for treating presbycusis. The technical progress of implantable hearing devices allows an effective hearing rehabilitation even in elderly with severe hearing loss. However, most people with hearing impairments are not treated adequately. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Prevention of Age-Related Macular Degeneration.

    Science.gov (United States)

    Singh, Niharika; Srinivasan, Sangeetha; Muralidharan, Vinata; Roy, Rupak; V, Jayprakash; Raman, Rajiv

    2017-01-01

    Age-related macular degeneration (AMD) compromises quality of life. However, the available therapeutic options are limited. This has led to the identification of modifiable risk factors to prevent the development or alter the natural course and prognosis of AMD. The identification and modification of risk factors has the potential for greater public health impact on reducing morbidity from AMD. Likewise, identifying the imaging clues and genetic clues could serve as a guide to recognizing the propensity for progression to severe and end stages of the disease. Several attempts, both successful and unsuccessful, have been made for interventions that could delay the progression of AMD. Of these, pharmacological interventions have shown promising results. The Age-Related Eye Disease Study 1 and 2 have shown the beneficial role of antioxidants in a selected group of patients. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

  16. Age-related macular degeneration

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    cause of blindness among Caucasian individuals in developed countries. Blindness resulting from AMD rarely occurs before age 70, and most cases occur after age 80. The age-standardised 1-year incidence of legal blindness resulting from AMD is 212 cases per million. Two-thirds of AMD cases have CNV......Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian...... individuals than in pigmented races. In predominantly Caucasian populations, the age-standardised prevalence of AMD in at least one eye is 7760 cases per million. The age-standardised cumulated 1-year incidence of AMD in at least one eye is 1051 cases per million individuals. AMD is the most important single...

  17. The metabolic profile of long-lived Drosophila melanogaster

    DEFF Research Database (Denmark)

    Sarup, Pernille Merete; Pedersen, Simon Metz Mariendal; Nielsen, Niels Chr

    2012-01-01

    We investigated the age-related changes in the metabolic profile of male Drosophila melanogaster and compared the metabolic profile of flies selected for increased longevity to that of control flies of equal age. We found clear differences in metabolite composition between selection regimes...

  18. [Age-related changes of sensory system].

    Science.gov (United States)

    Iwamoto, Toshihiko; Hanyu, Haruo; Umahara, Takahiko

    2013-10-01

    Pathological processes usually superimpose on physiological aging even in the sensory system including visual, hearing, olfactory, taste and somatosensory functions. Representative changes of age-related changes are presbyopia, cataracts, and presbyacusis. Reduced sense of smell is seen in normal aging, but the prominent reduction detected by the odor stick identification test is noticed especially in early stage of Alzheimer or Parkinson disease. Reduced sense of taste is well-known especially in salty sense, while the changes of sweet, bitter, and sour tastes are different among individuals. Finally, deep sensation of vibration and proprioception is decreased with age as well as superficial sensation (touch, temperature, pain). As a result, impaired sensory system could induce deterioration of the activities of daily living and quality of life in the elderly.

  19. Clinical and social characteristics associated with reduced visual acuity at presentation in Australian patients with neovascular age-related macular degeneration: a prospective study from a long-term observational data set. The Fight Retinal Blindness! Project.

    Science.gov (United States)

    Nguyen, Vuong; Daien, Vincent; Guymer, Robyn H; McAllister, Ian L; Morlet, Nigel; Barthelmes, Daniel; Gillies, Mark C

    2018-04-01

    Identifying variables that influence presenting visual acuity (VA) in patients with neovascular age-related macular degeneration (nAMD) is important because it is a strong predictor of long-term outcomes. To assess the clinical and social characteristics associated with low presenting VA in nAMD patients. The present study is a cross-sectional analysis from a prospective, observational database. We identified 3242 treatment-naïve patients from 54 Australian practices in the Fight Retinal Blindness! registry. Age, gender, ethnicity and VA were recorded at the baseline visit. Socio-economic status was determined using the Australian Bureau of Statistics socio-economic indexes for areas. Association between clinical and socio-economic characteristics with presenting VA was identified. Poor VA (≤35 letters) in the presenting eye was associated with older age (adjusted odds ratio [AOR]: 1.33 for patients aged ≥80 years vs. <80 years [95% confidence interval, CI: 1.04, 1.71]), treatment at a public practice (AOR: 1.91 for public vs. private practices [95% CI: 1.46, 2.50]) and intermediate (36-69 letters) VA in the fellow eye (AOR: 0.67 [95% CI: 0.47, 0.95] and 0.64 [95% CI: 0.48, 0.85] for poor [≤35 letters] and good [≥70 letters] VA vs. intermediate VA in the fellow eye). Gender, ethnicity and socio-economic status were not independently associated with VA at presentation. Poor presenting vision is detrimental to the long-term outcomes of nAMD. Poor presentation of nAMD in Australia may not be related to socio-economic circumstances, but due to systems of care. Further research is warranted to determine why patients at public practices present with worse vision compared with private practices in Australia. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

  20. Age-related hearing loss or presbycusis.

    Science.gov (United States)

    Huang, Qi; Tang, Jianguo

    2010-08-01

    Aging is a natural consequence of a society developing process. Although many adults retain good hearing as they aging, hearing loss related with age-presbycusis which can vary in severity from mild to substantial is common among elderly persons. There are a number of pathophysiological processes underlying age-related changes in the auditory system as well as in the central nervous systems. Many studies have been dedicated to the illustration of risk factors accumulating presbycusis such as heritability, environment factors, medical conditions, free radical (reactive oxygen species, ROS) and damage of mitochondrial DNA. Left untreated, presbycusis can not only lead sufferers to reduced quality of life, isolation, dependence and frustration, but also affect the healthy people around. These can be partly corrected using hearing aids, but it is not enough, more and more strategies of treatment based on the findings associating with presbycusis should be added rather than using single hearing aids. We review here the pathophysiology; heritability, susceptibility genes and other risk factors including environmental, medical, especially free radical (ROS) and damage of mitochondrial DNA; and some strategies of treatment, as well as promising rehabilitations associating with presbycusis.

  1. Age related macular degeneration and visual disability.

    Science.gov (United States)

    Christoforidis, John B; Tecce, Nicola; Dell'Omo, Roberto; Mastropasqua, Rodolfo; Verolino, Marco; Costagliola, Ciro

    2011-02-01

    substantial benefit in people with age-related macular degeneration. Prescription filters are one of the most beneficial visual aids that people with macular degeneration. In principle, one aims both at reducing short-wavelength light to reduce glare and at identifying light with specific wavelengths (colours) preferred by the patient for viewing. In both instances, such interventions result in apparent improved contrast sensitivity and better visual acuity. Although specific tests are performed to determine the best colour, tint, lens material, and type of frame for the patient's need, no scientific protocol has been developed so far to assist in prescribing tinted or selective transmission lenses . Magnifying optical lenses are available in a wide range of dioptric powers and are made from materials that correct for weight (plastic), thickness (high index), spherical aberrations (aspherical), and variable light intensities (photochromatic). These lenses can be used as loose lenses, mounted on optical frames, or used with a wide variety of attachments. As the dioptric power of plus lenses increases, the viewing distance of the target decreases, hence their usefulness mainly for tasks requiring near resolution acuity, like reading. Magnification can also be achieved with the use of telescopic devices that are built of two or more plus and (or) minus (minifying) optical lenses. Normal resolution acuity levels can be achieved with these devices for all viewing distances. Therefore, all telescopic devices are useful only for stationary patient tasks that do not require mobility and orientation. Electronic magnification has the great advantage over plus lenses of producing an acuity reserve enabling reading skills for almost all levels of visual acuity. The additional benefit provided is preservation of binocularity, even at high levels of visual disparity between the two eyes. Vision rehabilitation can help patients to maximize their remaining vision and adapt to activities of

  2. Transgenesis in Drosophila melanogaster.

    Science.gov (United States)

    Ringrose, Leonie

    2009-01-01

    Transgenesis in Drosophila melanogaster relies upon direct microinjection of embryos and subsequent crossing of surviving adults. The necessity of crossing single flies to screen for transgenic events limits the range of useful transgenesis techniques to those that have a very high frequency of integration, so that about 1 in 10 to 1 in 100 surviving adult flies carry a transgene. Until recently, only random P-element transgenesis fulfilled these criteria. However, recent advances have brought homologous recombination and site-directed integration up to and beyond this level of efficiency. For all transgenesis techniques in Drosophila melanogaster, microinjection of embryos is the central procedure. This chapter gives a detailed protocol for microinjection, and aims to enable the reader to use it for both site-directed integration and for P-element transgenesis.

  3. Extrinsic Mechanisms Involved in Age-Related Defective Bone Formation

    DEFF Research Database (Denmark)

    Trinquier, Anne Marie-Pierre Emilie; Kassem, Moustapha

    2011-01-01

    of fractures. Studies in rodents and humans revealed that, independent of sex hormone deficiency, the age-related decline in bone formation is characterized by decreased osteoblast number and lifespan and reduced bone-forming capacity of individual osteoblasts. An important clinical question is to identify...

  4. [New aspects in age related macular degeneration].

    Science.gov (United States)

    Turlea, C

    2012-01-01

    Being the leading cause of blindness in modern world Age Related Macular Degeneration has beneficiated in the last decade of important progress in diagnosis, classification and the discovery of diverse factors who contribute to the etiology of this disease. Treatments have arised who can postpone the irreversible evolution of the disease and thus preserve vision. Recent findings have identified predisposing genetic factors and also inflamatory and imunological parameters that can be modified trough a good and adequate prevention and therapy This articole reviews new aspects of patology of Age Related Macular Degeneration like the role of complement in maintaining inflamation and the role of oxidative stress on different structures of the retina.

  5. Neuromuscular contributions to age-related weakness

    Science.gov (United States)

    Age-related physiological change of neuromuscular function is not a linear process and is likely influenced by various biological and behavioral factors (e.g., genetics, nutrition, physical activity level, comorbidities, etc.). These factors contribute to heterogeneity among older adults, which chal...

  6. Epidemiology of age-related maculopathy

    NARCIS (Netherlands)

    J.R. Vingerling (Hans)

    1995-01-01

    textabstractIn 1875, Pagenstecher and Gentll provided the first description of age-related maculopathy (ARM). Nowadays, hundred and twenty years after the first description, ARM is one of the major causes of severe irreversible visual loss in the elderly in western countries. It has been estimated

  7. Folate and age-related disease

    NARCIS (Netherlands)

    Durga, J.

    2004-01-01

    Aging is associated with increased risk of cardiovascular and neurodegenerative disorders and an increase in their risk factors, such as decreased concentrations of folate and increased concentrations of homocysteine. The association of folate and homocysteine with age-related disease and, most

  8. Aging-related limit of exercise efficacy on motor decline

    Science.gov (United States)

    Arnold, Jennifer C.; Cantu, Mark A.; Kasanga, Ella A.; Nejtek, Vicki A.; Papa, Evan V.; Bugnariu, Nicoleta; Salvatore, Michael F.

    2017-01-01

    Identifying lifestyle strategies and allied neurobiological mechanisms that reduce aging-related motor impairment is imperative, given the accelerating number of retirees and increased life expectancy. A physically active lifestyle prior to old age can reduce risk of debilitating motor decline. However, if exercise is initiated after motor decline has begun in the lifespan, it is unknown if aging itself may impose a limit on exercise efficacy to decelerate further aging-related motor decline. In Brown-Norway/Fischer 344 F1 hybrid (BNF) rats, locomotor activity begins to decrease in middle age (12–18 months). One mechanism of aging-related motor decline may be decreased expression of GDNF family receptor, GFRα-1, which is decreased in substantia nigra (SN) between 12 and 30 months old. Moderate exercise, beginning at 18 months old, increases nigral GFRα-1 and tyrosine hydroxylase (TH) expression within 2 months. In aged rats, replenishing aging-related loss of GFRα-1 in SN increases TH in SN alone and locomotor activity. A moderate exercise regimen was initiated in sedentary male BNF rats in a longitudinal study to evaluate if exercise could attenuate aging-related motor decline when initiated at two different ages in the latter half of the lifespan (18 or 24 months old). Motor decline was reversed in the 18-, but not 24-month-old, cohort. However, exercise efficacy in the 18-month-old group was reduced as the rats reached 27 months old. GFRα-1 expression was not increased in either cohort. These studies suggest exercise can decelerate motor decline when begun in the latter half of the lifespan, but its efficacy may be limited by age of initiation. Decreased plasticity of GFRα-1 expression following exercise may limit its efficacy to reverse motor decline. PMID:29176896

  9. Interventions for age-related diseases

    DEFF Research Database (Denmark)

    Figueira, Inês; Fernandes, Adelaide; Mladenovic Djordjevic, Aleksandra

    2016-01-01

    Over 60% of people aged over 65 are affected by multiple morbidities, which are more difficult to treat, generate increased healthcare costs and lead to poor quality of life compared to individual diseases. With the number of older people steadily increasing this presents a societal challenge. Age...... is the major risk factor for age-related diseases and recent research developments have led to the proposal that pharmacological interventions targeting common mechanisms of ageing may be able to delay the onset of multimorbidity. Here we review the state of the knowledge of multimorbidity, appraise...... the available evidence supporting the role of mechanisms of ageing in the development of the most common age-related diseases and assess potential molecules that may successfully target those key mechanisms....

  10. CREB Overexpression Ameliorates Age-related Behavioral and Biophysical Deficits

    Science.gov (United States)

    Yu, Xiao-Wen

    Age-related cognitive deficits are observed in both humans and animals. Yet, the molecular mechanisms underlying these deficits are not yet fully elucidated. In aged animals, a decrease in intrinsic excitability of pyramidal neurons from the CA1 sub-region of hippocampus is believed to contribute to age-related cognitive impairments, but the molecular mechanism(s) that modulate both these factors has yet to be identified. Increasing activity of the transcription factor cAMP response element-binding protein (CREB) in young adult rodents has been shown to facilitate cognition, and increase intrinsic excitability of their neurons. However, how CREB changes with age, and how that impacts cognition in aged animals, is not clear. Therefore, we first systematically characterized age- and training-related changes in CREB levels in dorsal hippocampus. At a remote time point after undergoing behavioral training, levels of total CREB and activated CREB (phosphorylated at S133, pCREB) were measured in both young and aged rats. We found that pCREB, but not total CREB was significantly reduced in dorsal CA1 of aged rats. Importantly, levels of pCREB were found to be positively correlated with short-term spatial memory in both young and aged rats i.e. higher pCREB in dorsal CA1 was associated with better spatial memory. These findings indicate that an age-related deficit in CREB activity may contribute to the development of age-related cognitive deficits. However, it was still unclear if increasing CREB activity would be sufficient to ameliorate age-related cognitive, and biophysical deficits. To address this question, we virally overexpressed CREB in CA1, where we found the age-related deficit. Young and aged rats received control or CREB virus, and underwent water maze training. While control aged animals exhibited deficits in long-term spatial memory, aged animals with CREB overexpression performed at levels comparable to young animals. Concurrently, aged neurons

  11. Age-related hair pigment loss.

    Science.gov (United States)

    Tobin, Desmond J

    2015-01-01

    Humans are social animals that communicate disproportionately via potent genetic signals imbued in the skin and hair, including racial, ethnic, health, gender, and age status. For the vast majority of us, age-related hair pigment loss becomes the inescapable signal of our disappearing youth. The hair follicle (HF) pigmentary unit is a wonderful tissue for studying mechanisms generally regulating aging, often before this becomes evident elsewhere in the body. Given that follicular melanocytes (unlike those in the epidermis) are regulated by the hair growth cycle, this cycle is likely to impact the process of aging in the HF pigmentary unit. The formal identification of melanocyte stem cells in the mouse skin has spurred a flurry of reports on the potential involvement of melanocyte stem cell depletion in hair graying (i.e., canities). Caution is recommended, however, against simple extrapolation of murine data to humans. Regardless, hair graying in both species is likely to involve an age-related imbalance in the tissue's oxidative stress handling that will impact not only melanogenesis but also melanocyte stem cell and melanocyte homeostasis and survival. There is some emerging evidence that the HF pigmentary unit may have regenerative potential, even after it has begun to produce white hair fibers. It may therefore be feasible to develop strategies to modulate some aging-associated changes to maintain melanin production for longer. © 2015 S. Karger AG, Basel.

  12. Psychophysical function in age-related maculopathy.

    LENUS (Irish Health Repository)

    Neelam, Kumari

    2012-02-01

    Age-related macular degeneration (AMD), the late stage of age-related maculopathy (ARM), is the leading cause of blind registration in developed countries. The visual loss in AMD occurs due to dysfunction and death of photoreceptors (rods and cones) secondary to an atrophic or a neovascular event. The psychophysical tests of vision, which depend on the functional status of the photoreceptors, may detect subtle alterations in the macula before morphological fundus changes are apparent ophthalmoscopically, and before traditional measures of visual acuity exhibit deterioration, and may be a useful tool for assessing and monitoring patients with ARM. Furthermore, worsening of these visual functions over time may reflect disease progression, and some of these, alone or in combination with other parameters, may act as a prognostic indicator for identifying eyes at risk for developing neovascular AMD. Lastly, psychophysical tests often correlate with subjective and relatively undefined symptoms in patients with early ARM, and may reflect limitation of daily activities for ARM patients. However, clinical studies investigating psychophysical function have largely been cross-sectional in nature, with small sample sizes, and lack consistency in terms of the grading and classification of ARM. This article aims to comprehensively review the literature germane to psychophysical tests in ARM, and to furnish the reader with an insight into this complex area of research.

  13. Risk factors for age-related maculopathy.

    LENUS (Irish Health Repository)

    Connell, Paul P

    2012-02-01

    Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715\\/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.

  14. Age-related changes of monoaminooxidases in rat cerebellar cortex

    Directory of Open Access Journals (Sweden)

    FM Tranquilli Leali

    2009-06-01

    Full Text Available Age-related changes of the monoaminoxidases, evaluated by enzymatic staining, quantitative analysis of images, biochemical assay and statistical analysis of data were studied in cerebellar cortex of young (3-month-old and aged (26- month-old male Sprague-Dawley rats. The enzymatic staining shows the presence of monoamino-oxidases within the molecular and granular layers as well as within the Purkinje neurons of the cerebellum of young and aged animals. In molecular layer, and in Purkinje neurons the levels of monoaminooxidases were strongly increased in old rats. The granular layer showed, on the contrary, an age-dependent loss of enzymatic staining. These morphological findings were confirmed by biochemical results. The possibility that age-related changes in monoaminooxidase levels may be due to impaired energy production mechanisms and/or represent the consequence of reduced energetic needs is discussed.

  15. Ranibizumab vs. aflibercept for wet age-related macular degeneration

    DEFF Research Database (Denmark)

    Szabo, Shelagh M; Hedegaard, Morten; Chan, Keith

    2015-01-01

    the efficacy and safety of reduced frequency dosing for aflibercept, relative to other approved and marketed vascular endothelial growth factor inhibitors for wet AMD, over 12 months. RESEARCH DESIGN AND METHODS: Based on a systematic literature review performed according to a pre-specified protocol......OBJECTIVE: Although a reduced aflibercept (2.0 mg) injection frequency relative to the approved dosing posology is included in national treatment guidelines for wet age-related macular degeneration (AMD), there is limited evidence of its comparative efficacy. The objective was to compare...

  16. A synthetic combination of mutations, including fs(1)pyrSu(b), rSu(b) and b, causes female sterility and reduces embryonic viability in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Piskur, Jure; Gojkovic, Zoran; Bahn, E.

    1999-01-01

    A Drosophila melangaster mutant, fs(1)pyr(Su(b)), carrying a mutation that maps to the tip of the X chromosome, has been isolated. The mutation, when present alone, does not confer a detectable phenotype. However, this mutation causes female sterility and reduces embryonic viability when combined...

  17. Lifetime regular exercise affects the incident of different arrhythmias and improves organismal health in aging female Drosophila melanogaster.

    Science.gov (United States)

    Zheng, Lan; Li, Qiu Fang; Ni, Liu; Wang, Hui; Ruan, Xiang Cheng; Wu, Xiu Shan

    2017-02-01

    We used Drosophila melanogaster as an animal model system to study the impact of exercise training initiated early in life on cardiac function using a well-established model of inherent myogenic properties of the heart and discussed the changes on myosin, a myocardial contractile protein. We also explored the effect of early physical exercise on organismal aging by analyzing the wake-sleep pattern using a Drosophila activity monitor system. We found that a variety of arrhythmias are part of the heart spectrum in old flies after a lifetime of physical exercise as evidenced by reducing the incidence of fibrillations and increasing the occurrence of bradycardias. Maintenance of myocardial myosin levels may be an underlying contributor to these exercise-induced improvements in cardiac function at an advanced age. Moreover, we found that exercise training resulted in improved sleep quality by ameliorating age-related sleep inefficiency, fragmentation and sleep consolidation.

  18. Hhip haploinsufficiency sensitizes mice to age-related emphysema.

    Science.gov (United States)

    Lao, Taotao; Jiang, Zhiqiang; Yun, Jeong; Qiu, Weiliang; Guo, Feng; Huang, Chunfang; Mancini, John Dominic; Gupta, Kushagra; Laucho-Contreras, Maria E; Naing, Zun Zar Chi; Zhang, Li; Perrella, Mark A; Owen, Caroline A; Silverman, Edwin K; Zhou, Xiaobo

    2016-08-09

    Genetic variants in Hedgehog interacting protein (HHIP) have consistently been associated with the susceptibility to develop chronic obstructive pulmonary disease and pulmonary function levels, including the forced expiratory volume in 1 s (FEV1), in general population samples by genome-wide association studies. However, in vivo evidence connecting Hhip to age-related FEV1 decline and emphysema development is lacking. Herein, using Hhip heterozygous mice (Hhip(+/-)), we observed increased lung compliance and spontaneous emphysema in Hhip(+/-) mice starting at 10 mo of age. This increase was preceded by increases in oxidative stress levels in the lungs of Hhip(+/-) vs. Hhip(+/+) mice. To our knowledge, these results provide the first line of evidence that HHIP is involved in maintaining normal lung function and alveolar structures. Interestingly, antioxidant N-acetyl cysteine treatment in mice starting at age of 5 mo improved lung function and prevented emphysema development in Hhip(+/-) mice, suggesting that N-acetyl cysteine treatment limits the progression of age-related emphysema in Hhip(+/-) mice. Therefore, reduced lung function and age-related spontaneous emphysema development in Hhip(+/-) mice may be caused by increased oxidative stress levels in murine lungs as a result of haploinsufficiency of Hhip.

  19. Soybean β-Conglycinin Prevents Age-Related Hearing Impairment.

    Directory of Open Access Journals (Sweden)

    Tohru Tanigawa

    Full Text Available Obesity-related complications are associated with the development of age-related hearing impairment. β-Conglycinin (β-CG, one of the main storage proteins in soy, offers multiple health benefits, including anti-obesity and anti-atherosclerotic effects. Here, to elucidate the potential therapeutic application of β-CG, we investigated the effect of β-CG on age-related hearing impairment. Male wild-type mice (age 6 months were randomly divided into β-CG-fed and control groups. Six months later, the body weight was significantly lower in β-CG-fed mice than in the controls. Consumption of β-CG rescued the hearing impairment observed in control mice. Cochlear blood flow also increased in β-CG-fed mice, as did the expression of eNOS in the stria vascularis (SV, which protects vasculature. β-CG consumption also ameliorated oxidative status as assessed by 4-HNE staining. In the SV, lipofuscin granules of marginal cells and vacuolar degeneration of microvascular pericytes were decreased in β-CG-fed mice, as shown by transmission electron microscopy. β-CG consumption prevented loss of spiral ganglion cells and reduced the frequencies of lipofuscin granules, nuclear invaginations, and myelin vacuolation. Our observations indicate that β-CG ameliorates age-related hearing impairment by preserving cochlear blood flow and suppressing oxidative stress.

  20. Age-related changes in mastication.

    Science.gov (United States)

    Peyron, M A; Woda, A; Bourdiol, P; Hennequin, M

    2017-04-01

    The paper reviews human mastication, focusing on its age-related changes. The first part describes mastication adaptation in young healthy individuals. Adaptation to obtain a food bolus ready to be swallowed relies on variations in number of cycles, muscle strength and volume of emitted saliva. As a result, the food bolus displays granulometric and rheological properties, the values of which are maintained within the adaptive range of deglutition. The second part concerns healthy ageing. Some mastication parameters are slightly modified by age, but ageing itself does not impair mastication, as the adaptation possibilities remain operant. The third part reports on very aged subjects, who display frequent systemic or local diseases. Local and/or general diseases such as tooth loss, salivary defect, or motor impairment are then indistinguishably superimposed on the effects of very old age. The resulting impaired function increases the risk of aspiration and choking. Lastly, the consequences for eating behaviour and nutrition are evoked. © 2016 John Wiley & Sons Ltd.

  1. Radiotherapy in age-related macula degeneration

    International Nuclear Information System (INIS)

    Gripp, Stephan; Stammen, Johannes; Petersen, Claudia; Hartmann, Axel; Willers, Reinhart; Althaus, Christoph

    2002-01-01

    Purpose: To ascertain the benefit from radiotherapy in age-related macula degeneration in a single-arm longitudinal study. Methods and Materials: From 1997 to 1998, 39 patients with occult and 33 patients with classic choroidal neovascularization (CNV) were irradiated with 16 Gy. Fluorescein angiography and measurements of visual acuity were performed before and 3, 6, and 12 months after irradiation. Results: Complete follow-up data for 1 year were available from 69 patients. The mean patient age was 72 years (range 49-92). Vision decreased in 43, was stable in 18, and improved in 8 cases. The mean vision deteriorated significantly (p=0.02, Wilcoxon test), particularly within the first 3 months. Patients with occult CNV did significantly better than did those with classic CNV (p=0.03). The proportion of patients retaining vision ≥0.2 fell from 65% to 42% (p <0.01), for classic and occult CNV from 50% to 23%, and for occult CNV from 77% to 56% (p<0.02), respectively. CNV size increased in 30 patients and was stable in 38. Neither age (p=0.17) nor gender (p=0.21, chi-square test) influenced prognosis. Four patients reported transitional complaints. Conclusion: Low-dose fractionated radiotherapy with 16 Gy is well tolerated. However, vision and reading ability were not preserved in most patients

  2. Animal models of age related macular degeneration

    Science.gov (United States)

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

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  3. Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss

    Science.gov (United States)

    2012-07-01

    Mesenchymal stem cell (MSC) differentiation towards the bone forming osteoblastic lineage decreases as a function of age and may contribute to age-related...problem of age-related reduced availability of MSC we propose to examine the bone anabolic potential of induced pluripotent stem cell (iPS) derived MSC

  4. [Age-related decline of immune function and age-related diseases].

    Science.gov (United States)

    Isobe, Ken-ichi; Nishio, Naomi; Ito, Sachiko

    2009-07-01

    Effects of aging on immune system are widespread. The development of T and B cells declines with age. The functions of matured T and B cell also decline with age. Consequently, infections present major clinical problems for elderly patients. Many of age-related diseases are related to innate immunity. For example, the pathogenesis of atherosclerosis and Alzheimer disease are related to macrophages (microglia). The Ox-LDL or A-beta induces macrophages or microglia to produce inflammatory cytokines, chemokines and matrix metalloproteinases. Recently neutrophils have been shown to be an important immune cells in atherosclerosis. Neutrophils secrete inflammatory cytokines. In wound healing neutrophils also work as first important immune cells, which affect age-related decline of wound repair.

  5. Genetics Home Reference: age-related hearing loss

    Science.gov (United States)

    ... Description Age-related hearing loss (also known as presbycusis) is a decrease in hearing ability that happens ... age-related old-aged sensorineural hearing impairment presbyacusia presbycusis Related Information How are genetic conditions and genes ...

  6. NSAIDs may protect against age-related brain atrophy

    Directory of Open Access Journals (Sweden)

    Barbara B Bendlin

    2010-09-01

    Full Text Available The use of non-steroidal anti-inflammatory drugs (NSAIDs in humans is associated with brain differences including decreased number of activated microglia. In animals, NSAIDs are associated with reduced microglia, decreased amyloid burden, and neuronal preservation. Several studies suggest NSAIDs protect brain regions affected in the earliest stages of AD, including hippocampal and parahippocampal regions. In this cross-sectional study, we examined the protective effect of NSAID use on gray matter volume in a group of middle-aged and older NSAID users (n = 25 compared to non-user controls (n = 50. All participants underwent neuropsychological testing and T1-weighted magnetic resonance imaging. Non-user controls showed smaller volume in portions of the left hippocampus compared to NSAID users. Age-related loss of volume differed between groups, with controls showing greater medial temporal lobe volume loss with age compared to NSAID users. These results should be considered preliminary, but support previous reports that NSAIDs may modulate age-related loss of brain volume.

  7. Melatonin: Protection against age-related cardiac pathology.

    Science.gov (United States)

    Favero, Gaia; Franceschetti, Lorenzo; Buffoli, Barbara; Moghadasian, Mohammed H; Reiter, Russel J; Rodella, Luigi F; Rezzani, Rita

    2017-05-01

    Aging is a complex and progressive process that involves physiological and metabolic deterioration in every organ and system. Cardiovascular diseases are one of the most common causes of mortality and morbidity among elderly subjects worldwide. Most age-related cardiovascular disorders can be influenced by modifiable behaviours such as a healthy diet rich in fruit and vegetables, avoidance of smoking, increased physical activity and reduced stress. The role of diet in prevention of various disorders is a well-established factor, which has an even more important role in the geriatric population. Melatonin, an indoleamine with multiple actions including antioxidant properties, has been identified in a very large number of plant species, including edible plant products and medical herbs. Among products where melatonin has been identified include wine, olive oil, tomato, beer, and others. Interestingly, consumed melatonin in plant foods or melatonin supplementation may promote health benefits by virtue of its multiple properties and it may counteract pathological conditions also related to cardiovascular disorders, carcinogenesis, neurological diseases and aging. In the present review, we summarized melatonin effects against age-related cardiac alterations and abnormalities with a special focus on heart ischemia/reperfusion (IR) injury and myocardial infarction. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Radiation Therapy for Neovascular Age-related Macular Degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Kishan, Amar U. [Harvard Medical School, Boston, Massachusetts (United States); Modjtahedi, Bobeck S.; Morse, Lawrence S. [Department of Ophthalmology and Vision Sciences, University of California, Davis, Sacramento, California (United States); Lee, Percy, E-mail: percylee@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)

    2013-03-01

    In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity.

  9. Age-related associative deficits and the isolation effect.

    Science.gov (United States)

    Badham, Stephen P; Maylor, Elizabeth A

    2013-01-01

    If all but one of the items in a list are similar (e.g., all black except one red), memory for the different item is enhanced (the isolation effect). Older adults generally show similar or smaller isolation effects compared to young adults, which has been attributed to age-related deficits in associative memory whereby older adults are less able to associate an isolated stimulus to its isolating feature. Experiment 1 examined the isolation effect for isolation based on spatial position, modality and color; in Experiment 2, the criterion for isolation was the associative relation between stimuli. The results consistently showed no differences between young and older participants in the magnitude of the isolation effect. Whilst age deficits in associative memory may act to reduce the isolation effect in older adults, age deficits in self-initiated processing and inhibitory functionality may counteract this reduction by enhancing the isolation effect in older adults.

  10. Mapping of gene mutations in drosophila melanogaster

    OpenAIRE

    Halvorsen, Charlotte Marie

    2004-01-01

    In this experiment, mutant genes of a given unknown mutant strain of Drosophila melanogaster were mapped to specific chromosomes. Drosophila melanogaster, commonly known as the fruit fly, was the appropriate choice for the organism to use in this specific experiment because of its relatively rapid life cycle of 10-14 days and because of the small amount of space and food neccessary for maintaining thousands of flies. The D. Melanogaster unknown strain specifically used in this experiment wa...

  11. The Phenotypic Effects of Royal Jelly on Wild-Type D. melanogaster Are Strain-Specific.

    Directory of Open Access Journals (Sweden)

    Stefanie L Morgan

    Full Text Available The role for royal jelly (RJ in promoting caste differentiation of honeybee larvae into queens rather than workers is well characterized. A recent study demonstrated that this poorly understood complex nutrition drives strikingly similar phenotypic effects in Drosophila melanogaster, such as increased body size and reduced developmental time, making possible the use of D. melanogaster as a model system for the genetic analysis of the cellular mechanisms underlying RJ and caste differentiation. We demonstrate here that RJ increases the body size of some wild-type strains of D. melanogaster but not others, and report significant delays in developmental time in all flies reared on RJ. These findings suggest that cryptic genetic variation may be a factor in the D. melanogaster response to RJ, and should be considered when attempting to elucidate response mechanisms to environmental changes in non-honeybee species.

  12. Age-related variations of visuo-motor adaptation beyond explicit knowledge.

    Science.gov (United States)

    Heuer, Herbert; Hegele, Mathias

    2014-01-01

    Visuo-motor adaptation suffers at older working age. The age-related decline of behavioral adjustments is accompanied by reduced explicit knowledge of the visuo-motor transformation. It disappears when explicit knowledge is kept constant across the age range, except for particularly high levels of explicit knowledge. According to these findings, at older adult age both the acquisition of explicit knowledge and its application for strategic corrections become poorer. Recently it has been posited that visuo-motor adaptation can involve model-free reinforcement mechanisms of learning in addition to model-based mechanisms. We tested whether age-related declines of reinforcement learning can also contribute to the age-related changes of visuo-motor adaptation. Therefore we enhanced the contribution of reinforcement learning to visuo-motor adaptation by way of introducing salient markers of success and failure during practice. With such modified practice conditions, there were residual age-related variations of behavioral adjustments at all levels of explicit knowledge, even when explicit knowledge was absent. The residual age-related variations were observed for practiced target directions only, but not for new target directions. These findings are consistent with an age-related decline of model-free reinforcement learning as a third factor in the age-related decline of visuo-motor adaptation. Under practice conditions, which spur model-free reward-based learning, this factor adds to the decrements of the acquisition of explicit knowledge and its use for strategic corrections.

  13. Age-related variations of visuo-motor adaptation beyond explicit knowledge

    Directory of Open Access Journals (Sweden)

    Herbert eHeuer

    2014-07-01

    Full Text Available Visuo-motor adaptation suffers at older working age. The age-related decline of behavioural adjustments is accompanied by reduced explicit knowledge of the visuo-motor transformation. It disappears when explicit knowledge is kept constant across the age range, except for particularly high levels of explicit knowledge. According to these findings, at older adult age both the acquisition of explicit knowledge and its application for strategic corrections become poorer. Recently it has been posited that visuo-motor adaptation can involve model-free reinforcement mechanisms of learning in addition to model-based mechanisms. We tested whether age-related declines of reinforcement learning can also contribute to the age-related changes of visuo-motor adaptation. Therefore we enhanced the contribution of reinforcement learning to visuo-motor adaptation by way of introducing salient markers of success and failure during practice. With such modified practice conditions, there were residual age-related variations of behavioural adjustments at all levels of explicit knowledge, even when explicit knowledge was absent. The residual age-related variations were observed for practiced target directions only, but not for new target directions. These findings are consistent with an age-related decline of model-free reinforcement learning as a third factor in the age-related decline of visuo-motor adaptation. Under practice conditions, which spur model-free reward-based learning, this factor adds to the decrements of the acquisition of explicit knowledge and its use for strategic corrections.

  14. Adiponectin deficiency exacerbates age-related hearing impairment

    Science.gov (United States)

    Tanigawa, T; Shibata, R; Ouchi, N; Kondo, K; Ishii, M; Katahira, N; Kambara, T; Inoue, Y; Takahashi, R; Ikeda, N; Kihara, S; Ueda, H; Murohara, T

    2014-01-01

    Obesity-related disorders are closely associated with the development of age-related hearing impairment (ARHI). Adiponectin (APN) exerts protective effects against obesity-related conditions including endothelial dysfunction and atherosclerosis. Here, we investigated the impact of APN on ARHI. APN-knockout (APN-KO) mice developed exacerbation of hearing impairment, particularly in the high frequency range, compared with wild-type (WT) mice. Supplementation with APN prevented the hearing impairment in APN-KO mice. At 2 months of age, the cochlear blood flow and capillary density of the stria vascularis (SV) were significantly reduced in APN-KO mice as compared with WT mice. APN-KO mice also showed a significant increase in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells in the organ of Corti in the cochlea at 2 months of age. At the age of 6 months, hair cells were lost at the organ of Corti in APN-KO mice. In cultured auditory HEI-OC1 cells, APN reduced apoptotic activity under hypoxic conditions. Clinically, plasma APN levels were significantly lower in humans with ARHI. Multiple logistic regression analysis identified APN as a significant and independent predictor of ARHI. Our observations indicate that APN has an important role in preventing ARHI. PMID:24763046

  15. Prevalence of age-related macular degeneration in elderly Caucasians

    DEFF Research Database (Denmark)

    Erke, Maja G; Bertelsen, Geir; Peto, Tunde

    2012-01-01

    To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD).......To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD)....

  16. Impacts of age-related failures on nuclear systems

    International Nuclear Information System (INIS)

    Meale, B.M.; Satterwhite, D.G.; Krantz, E.A.; MacDonald, P.E.

    1986-01-01

    Aging-related failure data from nine light water reactor safety, support, and power conversion systems have been extracted from an operational data base. Systems and components within the systems that are most affected by aging are identified. In addition, information on aging-related root causes of component failures has been extracted for service water and Class 1E electrical power distribution systems. Engineering insights are presented, and preliminary quantification of the importance of aging-related root causes for a service water system is provided

  17. Progress on retinal image analysis for age related macular degeneration.

    Science.gov (United States)

    Kanagasingam, Yogesan; Bhuiyan, Alauddin; Abràmoff, Michael D; Smith, R Theodore; Goldschmidt, Leonard; Wong, Tien Y

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in those over the age of 50 years in the developed countries. The number is expected to increase by ∼1.5 fold over the next ten years due to an increase in aging population. One of the main measures of AMD severity is the analysis of drusen, pigmentary abnormalities, geographic atrophy (GA) and choroidal neovascularization (CNV) from imaging based on color fundus photograph, optical coherence tomography (OCT) and other imaging modalities. Each of these imaging modalities has strengths and weaknesses for extracting individual AMD pathology and different imaging techniques are used in combination for capturing and/or quantification of different pathologies. Current dry AMD treatments cannot cure or reverse vision loss. However, the Age-Related Eye Disease Study (AREDS) showed that specific anti-oxidant vitamin supplementation reduces the risk of progression from intermediate stages (defined as the presence of either many medium-sized drusen or one or more large drusen) to late AMD which allows for preventative strategies in properly identified patients. Thus identification of people with early stage AMD is important to design and implement preventative strategies for late AMD, and determine their cost-effectiveness. A mass screening facility with teleophthalmology or telemedicine in combination with computer-aided analysis for large rural-based communities may identify more individuals suitable for early stage AMD prevention. In this review, we discuss different imaging modalities that are currently being considered or used for screening AMD. In addition, we look into various automated and semi-automated computer-aided grading systems and related retinal image analysis techniques for drusen, geographic atrophy and choroidal neovascularization detection and/or quantification for measurement of AMD severity using these imaging modalities. We also review the existing telemedicine studies which

  18. Low Calorie Diet Affects Aging-Related Factors

    Science.gov (United States)

    ... Issue Past Issues Research News From NIH Low Calorie Diet Affects Aging-Related Factors Past Issues / Summer ... learn more about the effects of sustained low-calorie diets in humans on factors affecting aging. This ...

  19. [Depression in Patients with Age-Related Macular Degeneration].

    Science.gov (United States)

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  20. Risk factors of age-related macular degeneration in Argentina

    Directory of Open Access Journals (Sweden)

    María Eugenia Nano

    2013-04-01

    Full Text Available PURPOSES: To assess the risk factors of age-related macular degeneration in Argentina using a case-control study. METHODS: Surveys were used for subjects' antioxidant intake, age/gender, race, body mass index, hypertension, diabetes (and type of treatment, smoking, sunlight exposure, red meat consumption, fish consumption, presence of age-related macular degeneration and family history of age-related macular degeneration. Main effects models for logistic regression and ordinal logistic regression were used to analyze the results. RESULTS: There were 175 cases and 175 controls with a mean age of 75.4 years and 75.5 years, respectively, of whom 236 (67.4% were female. Of the cases with age-related macular degeneration, 159 (45.4% had age-related macular degeneration in their left eyes, 154 (44.0% in their right eyes, and 138 (39.4% in both eyes. Of the cases with age-related macular degeneration in their left eyes, 47.8% had the dry type, 40.3% had the wet type, and the type was unknown for 11.9%. The comparable figures for right eyes were: 51.9%, 34.4%, and 13.7%, respectively. The main effects model was dominated by higher sunlight exposure (OR [odds ratio]: 3.3 and a family history of age-related macular degeneration (OR: 4.3. Other factors included hypertension (OR: 2.1, smoking (OR: 2.2, and being of the Mestizo race, which lowered the risk of age-related macular degeneration (OR: 0.40. Red meat/fish consumption, body mass index, and iris color did not have an effect. Higher age was associated with progression to more severe age-related macular degeneration. CONCLUSION: Sunlight exposure, family history of age-related macular degeneration, and an older age were the significant risk factors. There may be other variables, as the risk was not explained very well by the existing factors. A larger sample may produce different and better results.

  1. Drosophila melanogaster gene expression changes after spaceflight.

    Data.gov (United States)

    National Aeronautics and Space Administration — Gene expression levels were determined in 3rd instar and adult Drosophila melanogaster reared during spaceflight to elucidate the genetic and molecular mechanisms...

  2. Ecdysteroid receptors in Drosophila melanogaster adult females

    Science.gov (United States)

    Ecdysteroid receptors were identified and partially characterized from total cell extracts of whole animals and dissected tissues from Drosophila melanogaster adult females. Binding studies indicated the presence of two ecdysteroid binding components having high affinity and specificity consistent w...

  3. Age-related changes in oscillatory power affect motor action.

    Directory of Open Access Journals (Sweden)

    Liqing Liu

    Full Text Available With increasing age cognitive performance slows down. This includes cognitive processes essential for motor performance. Additionally, performance of motor tasks becomes less accurate. The objective of the present study was to identify general neural correlates underlying age-related behavioral slowing and the reduction in motor task accuracy. To this end, we continuously recorded EEG activity from 18 younger and 24 older right-handed healthy participants while they were performing a simple finger tapping task. We analyzed the EEG records with respect to local changes in amplitude (power spectrum as well as phase locking between the two age groups. We found differences between younger and older subjects in the amplitude of post-movement synchronization in the β band of the sensory-motor and medial prefrontal cortex (mPFC. This post-movement β amplitude was significantly reduced in older subjects. Moreover, it positively correlated with the accuracy with which subjects performed the motor task at the electrode FCz, which detects activity of the mPFC and the supplementary motor area. In contrast, we found no correlation between the accurate timing of local neural activity, i.e. phase locking in the δ-θ frequency band, with the reaction and movement time or the accuracy with which the motor task was performed. Our results show that only post-movement β amplitude and not δ-θ phase locking is involved in the control of movement accuracy. The decreased post-movement β amplitude in the mPFC of older subjects hints at an impaired deactivation of this area, which may affect the cognitive control of stimulus-induced motor tasks and thereby motor output.

  4. Age-related changes in oscillatory power affect motor action.

    Science.gov (United States)

    Liu, Liqing; Rosjat, Nils; Popovych, Svitlana; Wang, Bin A; Yeldesbay, Azamat; Toth, Tibor I; Viswanathan, Shivakumar; Grefkes, Christian B; Fink, Gereon R; Daun, Silvia

    2017-01-01

    With increasing age cognitive performance slows down. This includes cognitive processes essential for motor performance. Additionally, performance of motor tasks becomes less accurate. The objective of the present study was to identify general neural correlates underlying age-related behavioral slowing and the reduction in motor task accuracy. To this end, we continuously recorded EEG activity from 18 younger and 24 older right-handed healthy participants while they were performing a simple finger tapping task. We analyzed the EEG records with respect to local changes in amplitude (power spectrum) as well as phase locking between the two age groups. We found differences between younger and older subjects in the amplitude of post-movement synchronization in the β band of the sensory-motor and medial prefrontal cortex (mPFC). This post-movement β amplitude was significantly reduced in older subjects. Moreover, it positively correlated with the accuracy with which subjects performed the motor task at the electrode FCz, which detects activity of the mPFC and the supplementary motor area. In contrast, we found no correlation between the accurate timing of local neural activity, i.e. phase locking in the δ-θ frequency band, with the reaction and movement time or the accuracy with which the motor task was performed. Our results show that only post-movement β amplitude and not δ-θ phase locking is involved in the control of movement accuracy. The decreased post-movement β amplitude in the mPFC of older subjects hints at an impaired deactivation of this area, which may affect the cognitive control of stimulus-induced motor tasks and thereby motor output.

  5. Age-related differences in cognition across the adult lifespan in autism spectrum disorder

    NARCIS (Netherlands)

    Lever, A.G.; Geurts, H.M.

    It is largely unknown how age impacts cognition in autism spectrum disorder (ASD). We investigated whether age-related cognitive differences are similar, reduced or increased across the adult lifespan, examined cognitive strengths and weaknesses, and explored whether objective test performance is

  6. Through thick and thin: A circulating growth factor inhibits age-related cardiac hypertrophy

    OpenAIRE

    McPherron, Alexandra C.

    2013-01-01

    In an intriguing new study, Loffredo et al., report that joining the circulation of old mice with that of young mice reduces age-related cardiac hypertrophy. They also found that the growth factor GDF11 is a circulating negative regulator of cardiac hypertrophy which suggests that raising GDF11 levels may be useful to treat cardiac hypertrophy associated with aging.

  7. Mechanisms of Age-Related Decline in Memory Search across the Adult Life Span

    Science.gov (United States)

    Hills, Thomas T.; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R.

    2013-01-01

    Three alternative mechanisms for age-related decline in memory search have been proposed, which result from either reduced processing speed (global slowing hypothesis), overpersistence on categories (cluster-switching hypothesis), or the inability to maintain focus on local cues related to a decline in working memory (cue-maintenance hypothesis).…

  8. Parainflammation, chronic inflammation, and age-related macular degeneration.

    Science.gov (United States)

    Chen, Mei; Xu, Heping

    2015-11-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration. © Society for Leukocyte Biology.

  9. Can DRYAD explain age-related associative memory deficits?

    Science.gov (United States)

    Smyth, Andrea C; Naveh-Benjamin, Moshe

    2016-02-01

    A recent interesting theoretical account of aging and memory judgments, the DRYAD (density of representations yields age-related deficits; Benjamin, 2010; Benjamin, Diaz, Matzen, & Johnson, 2012), attributes the extensive findings of disproportional age-related deficits in memory for source, context, and associations, to a global decline in memory fidelity. It is suggested that this global deficit, possibly due to a decline in attentional processes, is moderated by weak representation of contextual information to result in disproportional age-related declines. In the current article, we evaluate the DRYAD model, comparing it to specific age-related deficits theories, in particular, the ADH (associative deficit hypothesis, Naveh-Benjamin, 2000). We question some of the main assumptions/hypotheses of DRYAD in light of data reported in the literature, and we directly assess the role of attention in age-related deficits by manipulations of divided attention and of the instructions regarding what to pay attention to in 2 experiments (one from the literature and a new one). The results of these experiments fit the predictions of the ADH and do not support the main assumption/hypotheses of DRYAD. (c) 2016 APA, all rights reserved).

  10. Age-related inequalities in health and healthcare: the life stages approach.

    Science.gov (United States)

    Jecker, Nancy S

    2017-05-16

    How should healthcare systems prepare to care for growing numbers and proportions of older people? Older people generally suffer worse health than younger people do. Should societies take steps to reduce age-related health inequalities? Some express concern that doing so would increase age-related inequalities in healthcare. This paper addresses this debate by (1) presenting an argument in support of three principles for distributing scarce resources between age groups; (2) framing these principles of age group justice in terms of life stages; and (3) indicating policy implications that merit further attention in light of rapidly aging societies. © 2017 John Wiley & Sons Ltd.

  11. The Drosophila melanogaster host model

    Science.gov (United States)

    Igboin, Christina O.; Griffen, Ann L.; Leys, Eugene J.

    2012-01-01

    The deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, Drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen–host interactions of a wide variety of bacteria. These studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and Drosophila. This review presents an in-depth discussion of the Drosophila immune response, the Drosophila killing model, and the use of the model to examine bacterial–host interactions. The recent introduction of the Drosophila model into the oral microbiology field is discussed, specifically the use of the model to examine Porphyromonas gingivalis–host interactions, and finally the potential uses of this powerful model system to further elucidate oral bacterial-host interactions are addressed. PMID:22368770

  12. Gustatory Processing in Drosophila melanogaster.

    Science.gov (United States)

    Scott, Kristin

    2018-01-07

    The ability to identify nutrient-rich food and avoid toxic substances is essential for an animal's survival. Although olfaction and vision contribute to food detection, the gustatory system acts as a final checkpoint control for food acceptance or rejection. The vinegar fly Drosophila melanogaster tastes many of the same stimuli as mammals and provides an excellent model system for comparative studies of taste detection. The relative simplicity of the fly brain and behaviors, along with the molecular genetic and functional approaches available in this system, allow the examination of gustatory neural circuits from sensory input to motor output. This review discusses the molecules and cells that detect taste compounds in the periphery and the circuits that process taste information in the brain. These studies are providing insight into how the detection of taste compounds regulates feeding decisions.

  13. [Epidemiology of the age-related macular degeneration].

    Science.gov (United States)

    Kolár, P

    2010-07-01

    The age-related macular degeneration is the most common cause of severe decrease of the visual acuity in industrial countries. The epidemiological data published in last 30 years are very alarming. They document that the age-related macular degeneration is the most common cause of blindness in industrial countries in the population of patients older than 65 years. The signs of beginning disease may be diagnosed as early as in the patients older than 45 years. The disease is strictly age-related and its prevalence and incidence is markedly increasing according to the older age. The basic risk factors of the disease are smoking, untreated hypertension, atherosclerosis, cataract surgery, and appearance of the disease in the family. Among further possible risk factors we count diabetes mellitus and the light color of the iris. Equivocal is the negative influence of ultraviolet rays.

  14. Effect of polysaccharides extracted from Sipunculus nudus (SNP) on the lifespan and immune damage repair of Drosophila melanogaster exposed to Cd (VI).

    Science.gov (United States)

    Su, Jie; Jiang, Linlin; Wu, Jingna; Liu, Zhiyu; Wu, Yuping

    2017-06-26

    The water-soluble polysaccharides extracted from Sipunculus nudus (SNP) was investigated on the lifespan and immune damage repair of Drosophila melanogaster exposed to Cd (VI). SNP increased superoxyde dismutase (SOD), nitrogen monoxide (NO), glutathione peroxidase (GSH-Px) and total anti-oxidation competence (T-AOC), with decreased malondialdehyde (MDA) on D. melanogaster demonstrated that SNP could attenuate oxidative damage of D. melanogaster Exposed to Cd (VI). Real-time PCR and western blot analysis showed that SNP enhanced the gene expression of Diptericin, Drosomycin, Defensin, PGRP-LC and the protein level of Toll, p-JNK and Relish, that suggested the promoting effect of SNP on the immune damage repair of D. melanogaster exposed to Cd (VI). The increased level of Indy, Parkin and AMPK indicated the regulated effect of SNP on the longevity-related pathways through ageing-related moleculars of D. melanogaster exposed to Cd (VI). These results suggested that SNP could also improve the lifespan of D. melanogaster exposed to Cd (VI).

  15. Age-related changes in the cognitive function of sleep.

    Science.gov (United States)

    Pace-Schott, Edward F; Spencer, Rebecca M C

    2011-01-01

    Healthy aging is characterized by a diminished quality of sleep with decreased sleep duration and increased time awake after sleep onset. Older adults awaken more frequently and tend to awaken less from rapid eye movement (REM) sleep and more from non-REM (nREM) sleep than young adults. Sleep architecture also begins changing in middle age leading to a dramatic decrease in the deepest stage of nREM-slow wave sleep (SWS)-as aging progresses. Other less marked nREM changes include reduced numbers of sleep spindles and K-complexes. In contrast, the amount of REM diminishes only slightly. Both circadian and homeostatic sleep-regulatory processes are affected by aging. Circadian rhythms of temperature, melatonin, and cortisol are phase advanced and their amplitude diminished. An increased number of nocturnal awakenings and diminished daytime sleepiness suggest diminished homeostatic sleep pressure. A variety of endocrine and neuromodulatory changes (e.g., reduced growth hormone and dopamine levels) also accompany healthy aging. Healthy aging is characterized by declines in working memory and new episodic memory performance with relative sparing of semantic memory, recognition memory, and priming. Memory systems impacted by aging are associated with volumetric and functional changes in fronto-striatal circuits along with more limited changes in medial temporal structures (in which larger aging-related changes suggest neuropathology). Cross-sectional studies generally associate poorer sleep quality with poorer neuropsychological functioning. However, paradoxically, older adults appear to be more resistant to the cognitive effects of sleep deprivation, restriction, and fragmentation than younger adults. A new and expanding field examines the interaction between aging and sleep-dependent memory consolidation. Among forms of learning displaying prominent sleep-dependent consolidation in young adults, motor-sequence learning displays loss of sleep-dependent consolidation with

  16. Age-Related Eye Disease and Participation in Cognitive Activities

    OpenAIRE

    Varin, Melanie; Kergoat, Marie-Jeanne; Belleville, Sylvie; Li, Gisele; Rousseau, Jacqueline; Roy-Gagnon, Marie-Hélène; Moghadaszadeh, Solmaz; Freeman, Ellen E.

    2017-01-01

    Studies have found a benefit to living a cognitively active life in older age. Our goal was to quantify participation in cognitively stimulating activities in adults with and without age-related eye disease. We conducted a cross-sectional hospital-based study in Montreal, Canada of older adults (n = 303) having either age-related macular degeneration (AMD) (n = 96), glaucoma (n = 93), or normal vision (n = 114). To be eligible, the AMD group had to have bilateral late stage AMD with a better ...

  17. Behavioral Senescence and Aging-Related Changes in Motor Neurons and Brain Neuromodulator Levels Are Ameliorated by Lifespan-Extending Reproductive Dormancy in Drosophila

    Science.gov (United States)

    Liao, Sifang; Broughton, Susan; Nässel, Dick R.

    2017-01-01

    The lifespan of Drosophila melanogaster can be extended substantially by inducing reproductive dormancy (also known as diapause) by lowered temperature and short days. This increase of longevity is accompanied by lowered metabolism and increased stress tolerance. We ask here whether behavioral senescence is ameliorated during adult dormancy. To study this we kept flies for seven or more weeks in normal rearing conditions or in diapause conditions and compared to 1-week-old flies in different behavioral assays of sleep, negative geotaxis and exploratory walking. We found that the senescence of geotaxis and locomotor behavior seen under normal rearing conditions was negligible in flies kept in dormancy. The normal senescence of rhythmic activity and sleep patterns during the daytime was also reduced by adult dormancy. Investigating the morphology of specific neuromuscular junctions (NMJs), we found that changes normally seen with aging do not take place in dormant flies. To monitor age-associated changes in neuronal circuits regulating activity rhythms, sleep and walking behavior we applied antisera to tyrosine hydroxylase (TH), serotonin and several neuropeptides to examine changes in expression levels and neuron morphology. In most neuron types the levels of stored neuromodulators decreased during normal aging, but not in diapause treated flies. No signs of neurodegeneration were seen in either condition. Our data suggest that age-related changes in motor neurons could be the cause of part of the behavioral senescence and that this is ameliorated by reproductive diapause. Earlier studies established a link between age-associated decreases in neuromodulator levels and behavioral decline that could be rescued by overexpression of neuromodulator. Thus, it is likely that the retained levels of neuromodulators in dormant flies alleviate behavioral senescence. PMID:28503133

  18. Complement factor d in age-related macular degeneration

    NARCIS (Netherlands)

    Stanton, C.M.; Yates, J.R.W.; Hollander, A.I. den; Seddon, J.M.; Swaroop, A.; Stambolian, D.; Fauser, S.; Hoyng, C.B.; Yu, Y.; Atsuhiro, K.; Branham, K.; Othman, M.; Chen, W.; Kortvely, E.; Chalmers, K.; Hayward, C.; Moore, A.T.; Dhillon, B.; Ueffing, M.; Wright, A.F.

    2011-01-01

    Purpose. To examine the role of complement factor D (CFD) in age-related macular degeneration (AMD) by analysis of genetic association, copy number variation, and plasma CFD concentrations. Methods. Single nucleotide polymorphisms (SNPs) in the CFD gene were genotyped and the results analyzed by

  19. Age-related effects in the neocortical organization of chimpanzees

    DEFF Research Database (Denmark)

    Autrey, Michelle M; Reamer, Lisa A; Mareno, Mary Catherine

    2014-01-01

    Among primates, humans exhibit the most profound degree of age-related brain volumetric decline in particular regions, such as the hippocampus and the frontal lobe. Recent studies have shown that our closest living relatives, the chimpanzees, experience little to no volumetric decline in gray and...

  20. Translational strategies in aging and age-related disease

    NARCIS (Netherlands)

    Armanios, M.; Cabo, R. de; Mannick, J.; Partridge, L.; Deursen, J. van; Villeda, S.

    2015-01-01

    Aging is a risk factor for several of the world's most prevalent diseases, including neurodegenerative disorders, cancer, cardiovascular disease and metabolic disease. Although our understanding of the molecular pathways that contribute to the aging process and age-related disease is progressing

  1. Age-Related Hearing Loss: Implications for Counseling.

    Science.gov (United States)

    Souza, Pamela E.; Hoyer, William J.

    1996-01-01

    Examines adaptation strategies used by hearing-impaired listeners and considers the implications of age-related hearing loss for counseling, intervention, and self-management. Outlines information on hearing aids and on practical communication strategies and the growing importance of these strategies as the population grows increasingly older.…

  2. Current surgical treatment of age-related macular degeneration

    NARCIS (Netherlands)

    Ramos de Carvalho, J. Emanuel; Willig, A. J. H. E.; Chung, R.; Peiretti, E.; Mura, M.

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe, irreversible central vision loss in individuals over 65 years of age throughout much of the developed world. The advent of anti-VEGF therapy has had a great impact in the long-term natural history of this condition, more

  3. Nutritional influences on epigenetics and age-related disease

    Science.gov (United States)

    Nutritional epigenetics has emerged as a novel mechanism underlying gene–diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modu...

  4. Age-related decrements in cycling and running performance ...

    African Journals Online (AJOL)

    South African Journal of Sports Medicine ... This study examined age-related decrements in athletic performance during running and cycling activities. ... These findings establish a trend that there is 'accelerated' aging during running which can perhaps be attributed to the increased weight-bearing stress on the muscles ...

  5. Age-related macular degeneration in Onitsha, Nigeria | Nwosu ...

    African Journals Online (AJOL)

    Objectives: To determine the incidence, pattern and ocular morbidity associated with age-related macular degeneration (AMD) at the Guinness Eye Center Onitsha Nigeria. Materials and Methods: The case files of all new patients aged 50 years and above seen between January 1997 and December 2004 were reviewed.

  6. Age-related macular degeneration: epidemiology and optimal treatment

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian...

  7. Age-related differences in muscular capacity among workers

    NARCIS (Netherlands)

    Hamberg-van Reenen, H.H.; Beek, A.J. van der; Blatter, B.M.

    2009-01-01

    Purpose: To quantify the age-related changes in muscular capacity in a working population, and to investigate whether these changes are dependent on sports participation. Methods: Data were used from the longitudinal study on musculoskeletal disorders, absenteeism, stress and health (n = 1,800). At

  8. AGE-RELATED MACULAR DEGENERATION -AN EMERGING AND ...

    African Journals Online (AJOL)

    LIVINGSTON

    associatedwithwetmaculardegeneration . : Whites are much more at risk than Blacks . Age-related accumulation of low-molecular-weight phototoxic, pro-toxic melanin oligomers within the lysosomes in the retinal pigment epithelium are suspected of decreasing the digestive rate of photoreceptors of the outer rod segments ...

  9. Age-related decrements in cycling and running perfor- mance

    African Journals Online (AJOL)

    Enrique

    This study examined age-related decrements in athletic performance during running and cycling activi- ties. Design. The age group winning times for males aged between 18 and 70 years competing in the 1999 Argus cycle tour (103 km) and 1999 Comrades running marathon (90 km), South Africa's premier endurance.

  10. Age-related differences in women's foot shape

    NARCIS (Netherlands)

    Ansuategui Echeita, Jone; Hijmans, Juha M.; Smits, Sharon; Van der Woude, Lucas H. V.; Postema, Klaas

    2016-01-01

    Purpose: Describe age-related differences in women's foot shape using a wide range of measurements and ages. Study design: Cross-sectional, observational study. Main outcome measurements: Six foot-shape measurements of each foot: foot lengths, ball widths, ball circumferences, low instep

  11. Review Article Therapeutic Potential of Statins in Age-related ...

    African Journals Online (AJOL)

    2011-08-09

    Aug 9, 2011 ... ABSTRACT. Age-related macular degeneration (ARMD) is the leading cause of irreversible vision loss, affecting one in three people aged 75 and above. Although exciting new pharmaceuticals to treat ARMD such as endothelial growth factor (VEGF) inhibitors, are now available, they are effective only in ...

  12. Neuroimaging explanations of age-related differences in task performance

    Science.gov (United States)

    Steffener, Jason; Barulli, Daniel; Habeck, Christian; Stern, Yaakov

    2014-01-01

    Advancing age affects both cognitive performance and functional brain activity and interpretation of these effects has led to a variety of conceptual research models without always explicitly linking the two effects. However, to best understand the multifaceted effects of advancing age, age differences in functional brain activity need to be explicitly tied to the cognitive task performance. This work hypothesized that age-related differences in task performance are partially explained by age-related differences in functional brain activity and formally tested these causal relationships. Functional MRI data was from groups of young and old adults engaged in an executive task-switching experiment. Analyses were voxel-wise testing of moderated-mediation and simple mediation statistical path models to determine whether age group, brain activity and their interaction explained task performance in regions demonstrating an effect of age group. Results identified brain regions whose age-related differences in functional brain activity significantly explained age-related differences in task performance. In all identified locations, significant moderated-mediation relationships resulted from increasing brain activity predicting worse (slower) task performance in older but not younger adults. Findings suggest that advancing age links task performance to the level of brain activity. The overall message of this work is that in order to understand the role of functional brain activity on cognitive performance, analysis methods should respect theoretical relationships. Namely, that age affects brain activity and brain activity is related to task performance. PMID:24672481

  13. Neuroimaging explanations of age-related differences in task performance

    Directory of Open Access Journals (Sweden)

    Jason eSteffener

    2014-03-01

    Full Text Available Advancing age affects both cognitive performance and functional brain activity and interpretation of these effects has led to a variety of conceptual research models without always explicitly linking the two effects. However, to best understand the multifaceted effects of advancing age, age differences in functional brain activity need to be explicitly tied to the cognitive task performance. This work hypothesized that age-related differences in task performance are partially explained by age-related differences in functional brain activity and formally tested these causal relationships. Functional MRI data was from groups of young and old adults engaged in an executive task-switching experiment. Analyses were voxel-wise testing of moderated-mediation and simple mediation statistical path models to determine whether age group, brain activity and their interaction explained task performance in regions demonstrating an effect of age group. Results identified brain regions whose age-related differences in functional brain activity significantly explained age-related differences in task performance. In all identified locations, significant moderated-mediation relationships resulted from increasing brain activity predicting worse (slower task performance in older but not younger adults. Findings suggest that advancing age links task performance to the level of brain activity. The overall message of this work is that in order to understand the role of functional brain activity on cognitive performance, analysis methods should respect theoretical relationships. Namely, that age affects brain activity and brain activity is related to task performance.

  14. The molecular genetic basis of age-related macular degeneration ...

    Indian Academy of Sciences (India)

    Keywords. AMD; epidemiology; genes; polymorphism; risk. Abstract. Age-related macular degeneration (AMD) is a complex disorder of the eye and the third leading cause of blindness worldwide. With a multifactorial etiology, AMD results in progressive loss of central vision affecting the macular region of the eye in elderly.

  15. An epigenetic hypothesis of aging-related cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Marsha R Penner

    2010-03-01

    Full Text Available This brief review will focus on a new hypothesis for the role of epigenetic mechanisms in aging-related disruptions of synaptic plasticity and memory. Epigenetics refers to a set of potentially self-perpetuating, covalent modifications of DNA and post-translational modifications of nuclear proteins that produce lasting alterations in chromatin structure. These mechanisms, in turn, result in alterations in specific patterns of gene expression. Aging-related memory decline is manifest prominently in declarative/episodic memory and working memory, memory modalities anatomically based largely in the hippocampus and prefrontal cortex, respectively. The neurobiological underpinnings of age-related memory deficits include aberrant changes in gene transcription that ultimately affect the ability of the aged brain to be “plastic”. The molecular mechanisms underlying these changes in gene transcription are not currently known, but recent work points toward a potential novel mechanism, dysregulation of epigenetic mechanisms. This has led us to hypothesize that dysregulation of epigenetic control mechanisms and aberrant epigenetic “marks” drive aging-related cognitive dysfunction. Here we focus on this theme, reviewing current knowledge concerning epigenetic molecular mechanisms, as well as recent results suggesting disruption of plasticity and memory formation during aging. Finally, several open questions will be discussed that we believe will fuel experimental discovery.

  16. Gene-diet interactions in age-related macular degeneration

    Science.gov (United States)

    Age-related macular degeneration (AMD) is a prevalent blinding disease, accounting for roughly 50% of blindness in developed nations. Very significant advances have been made in terms of discovering genetic susceptibilities to AMD as well as dietary risk factors. To date, nutritional supplementation...

  17. Nutritional modulation of age-related macular degeneration

    Science.gov (United States)

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30-50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated wi...

  18. Awareness, Knowledge, and Concern about Age-Related Macular Degeneration

    Science.gov (United States)

    Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia

    2012-01-01

    Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-related…

  19. Therapeutic Potential of Statins in Age-related Macular Degeneration

    African Journals Online (AJOL)

    Age-related macular degeneration (ARMD) is the leading cause of irreversible vision loss, affecting one in three people aged 75 and above. Although exciting new pharmaceuticals to treat ARMD such as endothelial growth factor (VEGF) inhibitors, are now available, they are effective only in selected group of patients, and ...

  20. on visual acuity in age related macular degeneration

    African Journals Online (AJOL)

    marine origin) in the treatment of age related macular degeneration (AMD). In a randomized double blind clinical trial 280 eyes of 280 (157 F, 123 M) patients with wet and dry AMD were randomly assigned in treatment or placebo groups. Patients in ...

  1. The current pattern of gestational age-related anthropometric ...

    African Journals Online (AJOL)

    The current pattern of gestational age-related anthropometric parameters of term Nigerian neonates. O Oluwafemi,1 FWACP; F Njokanma,2 FWACP; E Disu,2 ... Weight and length at birth reflect the quality of intra-uterine growth and exert a strong influence on postnatal survival. ..... Neonatal anthropometry: The thin-fat.

  2. Prevalence of Age-Related Macular Degeneration in Europe

    NARCIS (Netherlands)

    Colijn, Johanna M.; Buitendijk, Gabriëlle H. S.; Prokofyeva, Elena; Alves, Dalila; Cachulo, Maria L.; Khawaja, Anthony P.; Cougnard-Gregoire, Audrey; Merle, Bénédicte M. J.; Korb, Christina; Erke, Maja G.; Bron, Alain; Anastasopoulos, Eleftherios; Meester-Smoor, Magda A.; Segato, Tatiana; Piermarocchi, Stefano; de Jong, Paulus T. V. M.; Vingerling, Johannes R.; Topouzis, Fotis; Creuzot-Garcher, Catherine; Bertelsen, Geir; Pfeiffer, Norbert; Fletcher, Astrid E.; Foster, Paul J.; Silva, Rufino; Korobelnik, Jean-François; Delcourt, Cécile; Klaver, Caroline C. W.; Ajana, Soufiane; Arango-Gonzalez, Blanca; Arndt, Verena; Bhatia, Vaibhav; Bhattacharya, Shomi S.; Biarnés, Marc; Borrell, Anna; Bühren, Sebastian; Calado, Sofia M.; Cougnard-Grégoire, Audrey; Dammeier, Sascha; de Jong, Eiko K.; de la Cerda, Berta; den Hollander, Anneke I.; Diaz-Corrales, Francisco J.; Diether, Sigrid; Emri, Eszter; Endermann, Tanja; Ferraro, Lucia L.; Garcia, Míriam; Heesterbeek, Thomas J.; Honisch, Sabina; Hoyng, Carel B.; Kersten, Eveline; Kilger, Ellen; Langen, Hanno; Lengyel, Imre; Luthert, Phil; Maugeais, Cyrille; Meester-Smoor, Magda; Monés, Jordi; Nogoceke, Everson; Peto, Tunde; Pool, Frances M.; Rodríguez, Eduardo; Ueffing, Marius; Ulrich Bartz-Schmidt, Karl U.; van Leeuwen, Elisabeth M.; Verzijden, Timo; Zumbansen, Markus; Acar, Niyazi; Anastosopoulos, Eleftherios; Azuara-Blanco, Augusto; Bergen, Arthur; Binquet, Christine; Bird, Alan; Brétillon, Lionel; Buitendijk, Gabrielle; Cachulo, Maria Luz; Chakravarthy, Usha; Chan, Michelle; Chang, Petrus; Colijn, Johanna; Cumberland, Philippa; Cunha-Vaz, José; Daien, Vincent; Deak, Gabor; Delyfer, Marie-Noëlle; den Hollander, Anneke; Dietzel, Martha; Erke, Maja Gran; Fauser, Sascha; Finger, Robert; Fletcher, Astrid; Foster, Paul; Founti, Panayiota; Göbel, Arno; Gorgels, Theo; Grauslund, Jakob; Grus, Franz; Hammond, Christopher; Helmer, Catherine; Hense, Hans-Werner; Hermann, Manuel; Hoehn, René; Hogg, Ruth; Holz, Frank; Hoyng, Carel; Jansonius, Nomdo; Janssen, Sarah; Khawaja, Anthony; Klaver, Caroline; Lamparter, Julia; Le Goff, Mélanie; Leal, Sergio; Lechanteur, Yara; Lehtimäki, Terho; Lotery, Andrew; Leung, Irene; Mauschitz, Matthias; Merle, Bénédicte; Meyer Zu Westrup, Verena; Midena, Edoardo; Miotto, Stefania; Mirshahi, Alireza; Mohan-Saïd, Sadek; Mueller, Michael; Muldrew, Alyson; Nunes, Sandrina; Oexle, Konrad; Rahi, Jugnoo; Raitakari, Olli; Ribeiro, Luisa; Rougier, Marie-Bénédicte; Sahel, José; Salonikiou, Aggeliki; Sanchez, Clarisa; Schmitz-Valckenberg, Steffen; Schweitzer, Cédric; Shehata, Jasmin; Silvestri, Giuliana; Simader, Christian; Souied, Eric; Springelkamp, Henriet; Tapp, Robyn; Verhoeven, Virginie; Von Hanno, Therese; Vujosevic, Stela; Williams, Katie; Wolfram, Christian; Yip, Jennifer; Zerbib, Jennyfer; Zwiener, Isabella

    2017-01-01

    Purpose: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in

  3. Prevalence of Age-Related Macular Degeneration in Europe

    DEFF Research Database (Denmark)

    Colijn, Johanna M; Buitendijk, Gabriëlle H S; Prokofyeva, Elena

    2017-01-01

    PURPOSE: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD...

  4. Pathophysiology of Age-Related Hearing Loss (Peripheral and Central)

    OpenAIRE

    Lee, Kyu-Yup

    2013-01-01

    Age-related hearing loss (presbycusis) refers to bilaterally symmetrical hearing loss resulting from aging process. Presbycusis is a complex phenomenon characterized by audiometric threshold shift, deterioration in speech-understanding and speech-perception difficulties in noisy environments. Factors contributing to presbycusis include mitochondria DNA mutation, genetic disorders including Ahl, hypertension, diabetes, metabolic disease and other systemic diseases in the intrinsic aspects. Ext...

  5. Age Related Variations in The Architecture of Caprine Haemal Nodes

    African Journals Online (AJOL)

    Age related variations in the architecture of caprine haemal nodes were studied in West African dwarf goats aged between 1-24 months. Variations were observed in the thickness of the capsule, the content and organization of the cortical and medullary parenchyma as well as the stroma. In young goats age between 1-4 ...

  6. Risks of age related macular degeneration and led lighting

    Directory of Open Access Journals (Sweden)

    V.A. Kaptsov

    2017-12-01

    Full Text Available Spectral structure of environmental light can have significant influence on risks of various eye diseases which can evolve quite early. The paper dwells on how age-related macular degeneration evolves and on a part which eye age pigment plays in the process. We discuss predictive models for age pigment accumulation and methodology of their creation. We created a predictive mathematical model for accumulated A2E age pigment quantity allowing for LED lighting peculiarities and its age-related perception. The model encompasses active oxygen forms generation evolving due to decrease in antioxidant cellular protection efficiency in a lighting environment with a higher blue light dose. It is shown that superoxide dismutase, catalase and glutathione peroxidase 1 (GRX 1 efficiency within 445 (plus minus 10 nanometers range drops substantially in blue light; it increases risks of lower cellular resistance to effects exerted by non-compensated active oxygen forms. These processes which are rather long-term can lead to early age-related macular degeneration. Mathematical calculations prove that in the nearest future a share of patients aged 30–40 who suffer from age-related macular degeneration will grow drastically; it will eventually lead to an increased number of disabled people aged 50–60 whose disability is caused by eyesight disorders. It is shown that if we fail to discover any mechanisms aimed at lowering risks of early age-related macular degeneration evolvement in the nearest future, total costs required for solving eyesight disorders issue will grow substantially. Thus, in 2012 about 140 billion dollars were spent on the eyesight disorders issue all over the world; the sum is likely to reach 377 billion dollars in 2050.

  7. Diastolic pressure underestimates age-related hemodynamic impairment.

    Science.gov (United States)

    Galarza, C R; Alfie, J; Waisman, G D; Mayorga, L M; Cámera, L A; del Río, M; Vasvari, F; Limansky, R; Farías, J; Tessler, J; Cámera, M I

    1997-10-01

    It has been hypothesized that as large arteries become more rigid with age, the pattern of hypertension changes from diastolic to systolic. Thus, diastolic blood pressure (DBP) may lose its ability to reflect the increase in vascular resistance with age. To assess this, we studied the age-related changes in blood pressure pattern and its steady-state and pulsatile determinants. We performed an epidemiological analysis based on a national survey of 10,462 subjects from Argentina. A hemodynamic analysis (impedance cardiography) was then carried out in 636 consecutive hypertensive patients (age, 25 to 74 years). Whereas the rate of increment in the prevalence of mild to moderate hypertension (MMH) reached a plateau after the sixth decade, isolated and borderline systolic forms of hypertension began a steep and sustained rise. Among patients with MMH, DBP remained stable from the third to the seventh decade, whereas SBP maintained a sustained increase. Despite similar DBP, the systemic vascular resistance index increased 47% (P<.01) and the cardiac index decreased 27% (P<.01), whereas the ratio of stroke volume to pulse pressure, an index of arterial compliance, decreased 45% (P<.01). However, there were no significant differences between older patients with MMH and those with isolated systolic hypertension in the level of SBP, vascular resistance, stroke volume, and cardiac index. Compared with age-matched normotensive control subjects, the ratio of stroke volume to pulse pressure was much more reduced in isolated systolic hypertension (48%) than in MMH (30%). In summary, the present study, carried out in a large sample of hypertensive subjects with a wide age range, showed a simultaneous impairment in vascular resistance and arterial compliance associated with aging in different patterns of hypertension. The magnitude of these changes, with opposite effects on DBP but additive effects on SBP, suggests that a hemodynamic mechanism could determine the transition in the

  8. Interleukin-13 and age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Bo Fu

    2017-04-01

    Full Text Available AIM: To identify the effects of interleukin (IL-13 on retinal pigment epithelial (RPE cells and the IL-13 level in aqueous humor of age-related macular degeneration (AMD patients. METHODS: IL-13 levels in aqueous humor specimens from AMD patients were detected with enzyme-linked immunosorbent assay (ELISA. ARPE-19 cells were treated with 10 ng/mL IL-13 for 12, 24, and 48h. The cell proliferaton was evaluated by the MTS method. The mRNA and protein levels of α-SMA and ZO-1 were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR and Western blot respectively. The expression of tumor necrosis factor-α (TNF-α, transforming growth factor-β (TGF-β and vascular endothelial growth factor (VEGF were assessed by ELISA. RESULTS: IL-13 levels in the aqueous humor of patients with AMD were significantly higher than those in the control (167.33±17.64 vs 27.12±5.65 pg/mL; P<0.01. In vitro, IL-13 of high concentrations (10, 15, and 20 ng/mL inhibited ARPE-19 cell proliferation. α-SMA mRNA in ARPE-19 cell were increased (1.017±0.112 vs 1.476±0.168; P<0.001 and ZO-1 decreased (1.051±0.136 vs 0.702±0.069; P<0.001 after treated with 10 ng/mL IL-13 for 48h. The protein expression of α-SMA and ZO-1 also showed the same tendency (α-SMA: P=0.038; ZO-1: P=0.008. IL-13 significantly reduced the level of TNF-α (44.70±1.67 vs 31.79±3.53 pg/mL; P=0.005 at 48h, but the level of TGF-β2 was significantly increased from 34.44±2.92 to 57.61±6.31 pg/mL at 24h (P=0.004 and from 61.26±1.11 to 86.91±3.59 pg/mL at 48h (P<0.001. While expressions of VEGF didn’t change after IL-13 treatment. CONCLUSION: IL-13 in vitro inhibit ARPE-19 cell proliferation and expression in the aqueous may be associated with AMD.

  9. Age-related differences in cognition across the adult lifespan in autism spectrum disorder.

    Science.gov (United States)

    Lever, Anne G; Geurts, Hilde M

    2016-06-01

    It is largely unknown how age impacts cognition in autism spectrum disorder (ASD). We investigated whether age-related cognitive differences are similar, reduced or increased across the adult lifespan, examined cognitive strengths and weaknesses, and explored whether objective test performance is related to subjective cognitive challenges. Neuropsychological tests assessing visual and verbal memory, generativity, and theory of mind (ToM), and a self-report measure assessing cognitive failures were administered to 236 matched participants with and without ASD, aged 20-79 years (IQ > 80). Group comparisons revealed that individuals with ASD had higher scores on visual memory, lower scores on generativity and ToM, and similar performance on verbal memory. However, ToM impairments were no longer present in older (50+ years) adults with ASD. Across adulthood, individuals with ASD demonstrated similar age-related effects on verbal memory, generativity, and ToM, while age-related differences were reduced on visual memory. Although adults with ASD reported many cognitive failures, those were not associated with neuropsychological test performance. Hence, while some cognitive abilities (visual and verbal memory) and difficulties (generativity and semantic memory) persist across adulthood in ASD, others become less apparent in old age (ToM). Age-related differences characteristic of typical aging are reduced or parallel, but not increased in individuals with ASD, suggesting that ASD may partially protect against an age-related decrease in cognitive functioning. Despite these findings, adults with ASD experience many cognitive daily challenges, which highlights the need for adequate social support and the importance of further research into this topic, including longitudinal studies. Autism Res 2016, 9: 666-676. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  10. Bowman-Birk inhibitor affects pathways associated with energy metabolism in Drosophila melanogaster

    Science.gov (United States)

    Bowman-Birk inhibitor (BBI) is toxic when fed to certain insects, including the fruit fly, Drosophila melanogaster. Dietary BBI has been demonstrated to slow growth and increase insect mortality by inhibiting the digestive enzymes trypsin and chymotrypsin, resulting in a reduced supply of amino acid...

  11. A data mining approach for classifying DNA repair genes into ageing-related or non-ageing-related

    Directory of Open Access Journals (Sweden)

    Vasieva Olga

    2011-01-01

    Full Text Available Abstract Background The ageing of the worldwide population means there is a growing need for research on the biology of ageing. DNA damage is likely a key contributor to the ageing process and elucidating the role of different DNA repair systems in ageing is of great interest. In this paper we propose a data mining approach, based on classification methods (decision trees and Naive Bayes, for analysing data about human DNA repair genes. The goal is to build classification models that allow us to discriminate between ageing-related and non-ageing-related DNA repair genes, in order to better understand their different properties. Results The main patterns discovered by the classification methods are as follows: (a the number of protein-protein interactions was a predictor of DNA repair proteins being ageing-related; (b the use of predictor attributes based on protein-protein interactions considerably increased predictive accuracy of attributes based on Gene Ontology (GO annotations; (c GO terms related to "response to stimulus" seem reasonably good predictors of ageing-relatedness for DNA repair genes; (d interaction with the XRCC5 (Ku80 protein is a strong predictor of ageing-relatedness for DNA repair genes; and (e DNA repair genes with a high expression in T lymphocytes are more likely to be ageing-related. Conclusions The above patterns are broadly integrated in an analysis discussing relations between Ku, the non-homologous end joining DNA repair pathway, ageing and lymphocyte development. These patterns and their analysis support non-homologous end joining double strand break repair as central to the ageing-relatedness of DNA repair genes. Our work also showcases the use of protein interaction partners to improve accuracy in data mining methods and our approach could be applied to other ageing-related pathways.

  12. The suprachiasmatic nucleus: age-related decline in biological rhythms.

    Science.gov (United States)

    Nakamura, Takahiro J; Takasu, Nana N; Nakamura, Wataru

    2016-09-01

    Aging is associated with changes in sleep duration and quality, as well as increased rates of pathologic/disordered sleep. While several factors contribute to these changes, emerging research suggests that age-related changes in the mammalian central circadian clock within the suprachiasmatic nucleus (SCN) may be a key factor. Prior work from our group suggests that circadian output from the SCN declines because of aging. Furthermore, we have previously observed age-related infertility in female mice, caused by a mismatch between environmental light-dark cycles and the intrinsic, internal biological clocks. In this review, we address regulatory mechanisms underlying circadian rhythms in mammals and summarize recent literature describing the effects of aging on the circadian system.

  13. Reviewing fluid systems for age-related degradation

    International Nuclear Information System (INIS)

    Smith, Stan

    1991-01-01

    Yankee Atomic Electric Company has developed the component degradation assessment tool (CoDAT), an expert system, that aids in handling and evaluating the large amounts of data required to support the license renewal process for nuclear power station fluid systems. In 1990, CoDAT evaluated the Yankee Nuclear Power Station fluid systems for age-related degradation. Its results are now being used to help focus the plant's maintenance programs and manage the expected degradation. CoDAT uses 'If-Then' rules, developed from industry codes, standards and publications, to determine the potential for 19 age-related degradation mechanisms. Other nuclear utilities pursuing the license renewal option also could use CoDAT. (author)

  14. Heart Failure as an Aging-Related Phenotype.

    Science.gov (United States)

    Morita, Hiroyuki; Komuro, Issei

    2018-01-27

    The molecular pathophysiology of heart failure, which is one of the leading causes of mortality, is not yet fully understood. Heart failure can be regarded as a systemic syndrome of aging-related phenotypes. Wnt/β-catenin signaling and the p53 pathway, both of which are key regulators of aging, have been demonstrated to play a critical role in the pathogenesis of heart failure. Circulating C1q was identified as a novel activator of Wnt/β-catenin signaling, promoting systemic aging-related phenotypes including sarcopenia and heart failure. On the other hand, p53 induces the apoptosis of cardiomyocytes in the failing heart. In these molecular mechanisms, the cross-talk between cardiomyocytes and non-cardiomyocytes (e,g,. endothelial cells, fibroblasts, smooth muscle cells, macrophages) deserves mentioning. In this review, we summarize recent advances in the understanding of the molecular pathophysiology underlying heart failure, focusing on Wnt/β-catenin signaling and the p53 pathway.

  15. Radiation treatment for age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Taniguchi, Tomoko; Mandai, Michiko; Honjo, Megumi; Matsuda, Naoko; Miyamoto, Hideki; Takahashi, Masayo; Ogura, Yuichiro; Sasai, Keisuke [Kyoto Univ. (Japan). Faculty of Medicine

    1996-11-01

    Fifteen eyes of age-related macular degeneration were treated by low-dose radiation. All the affected eyes had subfoveal neovascular membrane. Seventeen nontreated eyes with similar macular lesion served as control. Radiation was performed using photon beam at 6MV. Each eye received daily dose of 2 Gy for 5 consecutive days. When evaluated 9 to 12 months after treatment, the size of neovascular membrane had decreased in 47% of treated eyes and 7% of control eyes. The visual acuity improved by 2 lines or more in 13% of treated eyes and in none of control eyes. When the initial neovascular membrane was less than 1.5 disc diameter in size, the visual acuity had improved or remained stationary in 90% of treated eyes and in 36% of control eyes. The findings show the potential beneficial effect of radiation for age-related macular degeneration. (author)

  16. Age-related percutaneous penetration part 1: skin factors.

    Science.gov (United States)

    Konda, S; Meier-Davis, S R; Cayme, B; Shudo, J; Maibach, H I

    2012-05-01

    Changes in the skin that occur in the elderly may put them at increased risk for altered percutaneous penetration from pharmacotherapy along with potential adverse effects. Skin factors that may have a role in age-related percutaneous penetration include blood flow, pH, skin thickness, hair and pore density, and the content and structure of proteins, glycosaminoglycans (GAGs), water, and lipids. Each factor is examined as a function of increasing age along with its potential impact on percutaneous penetration. Additionally, topical drugs that successfully overcome the barrier function of the skin can still fall victim to cutaneous metabolism, thereby producing metabolites that may have increased or decreased activity. This overview discusses the current data and highlights the importance of further studies to evaluate the impact of skin factors in age-related percutaneous penetration.

  17. Humanin and age-related diseases: a new link?

    Science.gov (United States)

    Gong, Zhenwei; Tas, Emir; Muzumdar, Radhika

    2014-01-01

    Humanin (HN) is 24-amino acid mitochondria-associated peptide. Since its initial discovery over a decade ago, a role for HN has been reported in many biological processes such as apoptosis, cell survival, substrate metabolism, inflammatory response, and response to stressors such as oxidative stress, ischemia, and starvation. HN and its potent analogs have been shown to have beneficial effects in many age-related diseases including Alzheimer's disease, stroke, diabetes, myocardial ischemia and reperfusion, atherosclerosis, amyotrophic lateral sclerosis, and certain types of cancer both in vitro and in vivo. More recently, an association between HN levels, growth hormone/insulin-like growth factor-1 (GH/IGF axis), and life span was demonstrated using various mouse models with mutations in the GH/IGF axis. The goal of this review is to summarize the current understanding of the role of HN in aging and age-related diseases.

  18. Humanin and Age-related diseases: A new link?

    Directory of Open Access Journals (Sweden)

    Zhenwei eGong

    2014-12-01

    Full Text Available Humanin (HN is 24-amino acid mitochondria-associated peptide. Since its initial discovery over a decade ago, a role for HN has been reported in many biological processes such as apoptosis, cell survival, substrate metabolism, inflammatory response and response to stressors such as oxidative stress, ischemia and starvation. HN and its potent analogs have been shown to have beneficial effects in many age-related diseases including Alzheimer’s disease (AD, stroke, diabetes, myocardial ischemia and reperfusion (MI-R, atherosclerosis, amyotrophic lateral sclerosis (ALS and certain types of cancer both in vitro and in vivo. More recently, an association between HN levels, growth hormone/ insulin-like growth factor-1 (GH/IGF axis and life span was demonstrated using various mouse models with mutations in the GH/IGF axis. The goal of this review is to summarize the current understanding of the role of HN in aging and age-related diseases.

  19. Lipids, Lipoproteins, and Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Katayoon B. Ebrahimi

    2011-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness among the elderly. While excellent treatment has emerged for neovascular disease, treatment for early AMD is lacking due to an incomplete understanding of the early molecular events. A prominent age-related change is the accumulation of neutral lipid in normal Bruch's membrane (BrM throughout adulthood and also disease-related BrM accumulations called basal deposits and drusen. AMD lesion formation has thus been conceptualized as sharing mechanisms with atherosclerotic plaque formation, where low-density lipoprotein (LDL retention within the arterial wall initiates a cascade of pathologic events. However, we do not yet understand how lipoproteins contribute to AMD. This paper explores how systemic and local production of lipoproteins might contribute to the pathogenesis of AMD.

  20. eNOS-uncoupling in age-related erectile dysfunction

    OpenAIRE

    Johnson, JM; Bivalacqua, TJ; Lagoda, GA; Burnett, AL; Musicki, B

    2011-01-01

    Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH4) on erectile function in the aged rats. Male Fischer 344 ...

  1. Complement pathway biomarkers and age-related macular degeneration

    Science.gov (United States)

    Gemenetzi, M; Lotery, A J

    2016-01-01

    In the age-related macular degeneration (AMD) ‘inflammation model', local inflammation plus complement activation contributes to the pathogenesis and progression of the disease. Multiple genetic associations have now been established correlating the risk of development or progression of AMD. Stratifying patients by their AMD genetic profile may facilitate future AMD therapeutic trials resulting in meaningful clinical trial end points with smaller sample sizes and study duration. PMID:26493033

  2. Senescent cells: SASPected drivers of age-related pathologies.

    Science.gov (United States)

    Ovadya, Yossi; Krizhanovsky, Valery

    2014-12-01

    The progression of physiological ageing is driven by intracellular aberrations including telomere attrition, genomic instability, epigenetic alterations and loss of proteostasis. These in turn damage cells and compromise their functionality. Cellular senescence, a stable irreversible cell-cycle arrest, is elicited in damaged cells and prevents their propagation in the organism. Under normal conditions, senescent cells recruit the immune system which facilitates their removal from tissues. Nevertheless, during ageing, tissue-residing senescent cells tend to accumulate, and might negatively impact their microenvironment via profound secretory phenotype with pro-inflammatory characteristics, termed senescence-associated secretory phenotype (SASP). Indeed, senescent cells are mostly abundant at sites of age-related pathologies, including degenerative disorders and malignancies. Interestingly, studies on progeroid mice indicate that selective elimination of senescent cells can delay age-related deterioration. This suggests that chronic inflammation induced by senescent cells might be a main driver of these pathologies. Importantly, senescent cells accumulate as a result of deficient immune surveillance, and their removal is increased upon the use of immune stimulatory agents. Insights into mechanisms of senescence surveillance could be combined with current approaches for cancer immunotherapy to propose new preventive and therapeutic strategies for age-related diseases.

  3. Identification of Age-Related Macular Degeneration Using OCT Images

    Science.gov (United States)

    Arabi, Punal M., Dr; Krishna, Nanditha; Ashwini, V.; Prathibha, H. M.

    2018-02-01

    Age-related Macular Degeneration is the most leading retinal disease in the recent years. Macular degeneration occurs when the central portion of the retina, called macula deteriorates. As the deterioration occurs with the age, it is commonly referred as Age-related Macular Degeneration. This disease can be visualized by several imaging modalities such as Fundus imaging technique, Optical Coherence Tomography (OCT) technique and many other. Optical Coherence Tomography is the widely used technique for screening the Age-related Macular Degeneration disease, because it has an ability to detect the very minute changes in the retina. The Healthy and AMD affected OCT images are classified by extracting the Retinal Pigmented Epithelium (RPE) layer of the images using the image processing technique. The extracted layer is sampled, the no. of white pixels in each of the sample is counted and the mean value of the no. of pixels is calculated. The average mean value is calculated for both the Healthy and the AMD affected images and a threshold value is fixed and a decision rule is framed to classify the images of interest. The proposed method showed an accuracy of 75%.

  4. Age-related differences in working memory updating components.

    Science.gov (United States)

    Linares, Rocío; Bajo, M Teresa; Pelegrina, Santiago

    2016-07-01

    The aim of this study was to investigate possible age-related changes throughout childhood and adolescence in different component processes of working memory updating (WMU): retrieval, transformation, and substitution. A set of numerical WMU tasks was administered to four age groups (8-, 11-, 14-, and 21-year-olds). To isolate the effect of each of the WMU components, participants performed different versions of a task that included different combinations of the WMU components. The results showed an expected overall decrease in response times and an increase in accuracy performance with age. Most important, specific age-related changes in the retrieval component were found, demonstrating that the effect of retrieval on accuracy was larger in children than in adolescents or young adults. These findings indicate that the availability of representations from outside the focus of attention may change with age. Thus, the retrieval component of updating could contribute to the age-related changes observed in the performance of many updating tasks. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Proteome reference map of Drosophila melanogaster head.

    Science.gov (United States)

    Lee, Tian-Ren; Huang, Shun-Hong; Lee, Chi-Ching; Lee, Hsiao-Yun; Chan, Hsin-Tzu; Lin, Kuo-Sen; Chan, Hong-Lin; Lyu, Ping-Chiang

    2012-06-01

    Drosophila melanogaster has been used as a genetic model organism to understand the fundamental molecular mechanisms in human biology including memory formation that has been reported involving protein synthesis and/or post-translational modification. In this study, we employed a proteomic platform based on fluorescent 2DE and MALDI-TOF MS to build a standard D. melanogaster head proteome map for proteome-proteome comparison. In order to facilitate the comparison, an interactive database has been constructed for systematically integrating and analyzing the proteomes from different conditions and further implicated to study human diseases related to D. melanogaster model. In summary, the fundamental head proteomic database and bioinformatic analysis will be useful for further elucidating the biological mechanisms such as memory formation and neurodegenerative diseases. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Age-related epigenetic drift and phenotypic plasticity loss: implications in prevention of age-related human diseases.

    Science.gov (United States)

    Li, Yuanyuan; Tollefsbol, Trygve O

    2016-12-01

    Aging is considered as one of the most important developmental processes in organisms and is closely associated with global deteriorations of epigenetic markers such as aberrant methylomic patterns. This altered epigenomic state, referred to 'epigenetic drift', reflects deficient maintenance of epigenetic marks and contributes to impaired cellular and molecular functions in aged cells. Epigenetic drift-induced abnormal changes during aging are scantily repaired by epigenetic modulators. This inflexibility in the aged epigenome may lead to an age-related decline in phenotypic plasticity at the cellular and molecular levels due to epigenetic drift. This perspective aims to provide novel concepts for understanding epigenetic effects on the aging process and to provide insights into epigenetic prevention and therapeutic strategies for age-related human disease.

  7. Physical Activity and Telomere Biology: Exploring the Link with Aging-Related Disease Prevention

    Directory of Open Access Journals (Sweden)

    Andrew T. Ludlow

    2011-01-01

    Full Text Available Physical activity is associated with reduced risk of several age-related diseases as well as with increased longevity in both rodents and humans. Though these associations are well established, evidence of the molecular and cellular factors associated with reduced disease risk and increased longevity resulting from physical activity is sparse. A long-standing hypothesis of aging is the telomere hypothesis: as a cell divides, telomeres shorten resulting eventually in replicative senescence and an aged phenotype. Several reports have recently associated telomeres and telomere-related proteins to diseases associated with physical inactivity and aging including cardiovascular disease, insulin resistance, and hypertension. Interestingly several reports have also shown that longer telomeres are associated with higher physical activity levels, indicating a potential mechanistic link between physical activity, reduced age-related disease risk, and longevity. The primary purpose of this review is to discuss the potential importance of physical activity in telomere biology in the context of inactivity- and age-related diseases. A secondary purpose is to explore potential mechanisms and important avenues for future research in the field of telomeres and diseases associated with physical inactivity and aging.

  8. Cognitive impairment in the Age-Related Eye Disease Study: AREDS report no. 16.

    Science.gov (United States)

    Clemons, Traci E; Rankin, Molly W; McBee, Wendy L

    2006-04-01

    To investigate potential associations between cognitive function and/or impairment and age-related macular degeneration (AMD) and visual impairment in the Age-Related Eye Disease Study (AREDS). The AREDS is an 11-center natural history study of AMD and age-related cataract. The AREDS Cognitive Function Battery was administered to 2946 participants. The battery consists of 6 neuropsychological tests measuring performance in several cognitive domains. The Dunnett multiple comparison test was used to identify differences by AMD and visual acuity severity. The relationship with cognitive impairment was also assessed using logistic regression. Mean scores of instruments in the AREDS Cognitive Function Battery declined with increased macular abnormalities and reduced visual acuity. After adjustment for age, sex, race, education, smoking status, diabetes mellitus, hypertension, and depression, increased macular abnormalities (trend P value cognitive function scores as measured by the Modified Mini-Mental State Examination and the Wechsler Logical Memory Scale. Reduced vision was found to be associated with reduced mean cognitive function scores as measured by the Modified Mini-Mental State Examination and letter and verbal fluency tasks. Persons with vision worse than 20/40 OU were more likely to be cognitively impaired (Modified Mini-Mental State Examination score cognitive impairment in older persons.

  9. Endosymbiont-based immunity in Drosophila melanogaster against parasitic nematode infection.

    Science.gov (United States)

    Yadav, Shruti; Frazer, Joanna; Banga, Ashima; Pruitt, Katherine; Harsh, Sneh; Jaenike, John; Eleftherianos, Ioannis

    2018-01-01

    Associations between endosymbiotic bacteria and their hosts represent a complex ecosystem within organisms ranging from humans to protozoa. Drosophila species are known to naturally harbor Wolbachia and Spiroplasma endosymbionts, which play a protective role against certain microbial infections. Here, we investigated whether the presence or absence of endosymbionts affects the immune response of Drosophila melanogaster larvae to infection by Steinernema carpocapsae nematodes carrying or lacking their mutualistic Gram-negative bacteria Xenorhabdus nematophila (symbiotic or axenic nematodes, respectively). We find that the presence of Wolbachia alone or together with Spiroplasma promotes the survival of larvae in response to infection with S. carpocapsae symbiotic nematodes, but not against axenic nematodes. We also find that Wolbachia numbers are reduced in Spiroplasma-free larvae infected with axenic compared to symbiotic nematodes, and they are also reduced in Spiroplasma-containing compared to Spiroplasma-free larvae infected with axenic nematodes. We further show that S. carpocapsae axenic nematode infection induces the Toll pathway in the absence of Wolbachia, and that symbiotic nematode infection leads to increased phenoloxidase activity in D. melanogaster larvae devoid of endosymbionts. Finally, infection with either type of nematode alters the metabolic status and the fat body lipid droplet size in D. melanogaster larvae containing only Wolbachia or both endosymbionts. Our results suggest an interaction between Wolbachia endosymbionts with the immune response of D. melanogaster against infection with the entomopathogenic nematodes S. carpocapsae. Results from this study indicate a complex interplay between insect hosts, endosymbiotic microbes and pathogenic organisms.

  10. Age-related degradation of Westinghouse 480-volt circuit breakers

    International Nuclear Information System (INIS)

    Subudhi, M.; Shier, W.; MacDougall, E.

    1990-07-01

    An aging assessment of Westinghouse DS-series low-voltage air circuit breakers was performed as part of the Nuclear Plant Aging Research (NPAR) program. The objectives of this study are to characterize age-related degradation within the breaker assembly and to identify maintenance practices to mitigate their effect. Since this study has been promulgated by the failures of the reactor trip breakers at the McGuire Nuclear Station in July 1987, results relating to the welds in the breaker pole lever welds are also discussed. The design and operation of DS-206 and DS-416 breakers were reviewed. Failure data from various national data bases were analyzed to identify the predominant failure modes, causes, and mechanisms. Additional operating experiences from one nuclear station and two industrial breaker-service companies were obtained to develop aging trends of various subcomponents. The responses of the utilities to the NRC Bulletin 88-01, which discusses the center pole lever welds, were analyzed to assess the final resolution of failures of welds in the reactor trips. Maintenance recommendations, made by the manufacturer to mitigate age-related degradation were reviewed, and recommendations for improving the monitoring of age-related degradation are discussed. As described in Volume 2 of this NUREG, the results from a test program to assess degradation in breaker parts through mechanical cycling are also included. The testing has characterized the cracking of center-pole lever welds, identified monitoring techniques to determine aging in breakers, and provided information to augment existing maintenance programs. Recommendations to improve breaker reliability using effective maintenance, testing, and inspection programs are suggested. 13 refs., 21 figs., 8 tabs

  11. Age-related decline in perception of prosodic affect.

    Science.gov (United States)

    Kiss, I; Ennis, T

    2001-01-01

    Perception of affect in speech is an important aspect of language, often conveying more about the intent of the speaker than semantic content. Impairment of perception of affect is seen in patients with right-hemisphere lesions. Nevertheless, little attention is paid to perception of emotional prosody in clinical neuropsychology. We present data concerning a revised version of the Emotional Perception Test (EPT-R), which indicates that older participants are significantly worse in prosodic perception than IQ-matched younger participants. The apparent age-related differences in perception of prosody are similar in magnitude to those seen on memory tests.

  12. Research status of conbercept treating age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Hai-Yan He

    2015-08-01

    Full Text Available Age-related macular degeneration(AMDis one of the major reasons of blindness among the elderly in the developed countries. As AMD patients are increasing year by year, AMD has become one of the important topics of ophthalmic research to prevent blindness. Its pathogenesis is not fully understood, but many studies have shown that vascular endothelial growth factor(VEGFplays an important role in the pathogenesis. With the development and application of anti-VEGF drugs, there are a variety of drugs applied to the disease. This article introduces conbercept for the treatment of AMD.

  13. The DrugAge database of aging-related drugs.

    Science.gov (United States)

    Barardo, Diogo; Thornton, Daniel; Thoppil, Harikrishnan; Walsh, Michael; Sharifi, Samim; Ferreira, Susana; Anžič, Andreja; Fernandes, Maria; Monteiro, Patrick; Grum, Tjaša; Cordeiro, Rui; De-Souza, Evandro Araújo; Budovsky, Arie; Araujo, Natali; Gruber, Jan; Petrascheck, Michael; Fraifeld, Vadim E; Zhavoronkov, Alexander; Moskalev, Alexey; de Magalhães, João Pedro

    2017-06-01

    Aging is a major worldwide medical challenge. Not surprisingly, identifying drugs and compounds that extend lifespan in model organisms is a growing research area. Here, we present DrugAge (http://genomics.senescence.info/drugs/), a curated database of lifespan-extending drugs and compounds. At the time of writing, DrugAge contains 1316 entries featuring 418 different compounds from studies across 27 model organisms, including worms, flies, yeast and mice. Data were manually curated from 324 publications. Using drug-gene interaction data, we also performed a functional enrichment analysis of targets of lifespan-extending drugs. Enriched terms include various functional categories related to glutathione and antioxidant activity, ion transport and metabolic processes. In addition, we found a modest but significant overlap between targets of lifespan-extending drugs and known aging-related genes, suggesting that some but not most aging-related pathways have been targeted pharmacologically in longevity studies. DrugAge is freely available online for the scientific community and will be an important resource for biogerontologists. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  14. Age-related changes in crowding and reading speed.

    Science.gov (United States)

    Liu, Rong; Patel, Bhavika N; Kwon, MiYoung

    2017-08-15

    Crowding, the inability to recognize objects in clutter, is known to play a role in developmental changes in reading speed. Here, we investigated whether crowding also plays a role in age-related changes in reading speed. We recruited 18 young (mean age: 22.6 ± 3.5; range: 18~31) and 21 older adults (mean age: 58.2 ± 7.0; range: 50~73) with normal vision. Reading speed was measured with short blocks of text. The degree of crowding was determined by measuring crowding zone (the distance between a target and flankers required to yield a criterion recognition accuracy) and the size of the visual span (an uncrowded window in the visual field within which letters can be recognizable reliably). Measurements were made across the central 16-degree visual field using letter-recognition tasks. Our results showed that, compared to young adults, older adults exhibited significantly slower reading speed (a decrease by 30%) and larger crowding: an enlargement of crowding zone (an increase by 31%) and shrinkage of the visual span (a decrease by 6.25 bits). We also observed significant correlations between reading speed and each of the crowding measures. Our results suggest that crowding increases with age. Age-related changes in crowding may in part explain slower reading in older adults.

  15. Age-related changes in the knee meniscus.

    Science.gov (United States)

    Tsujii, Akira; Nakamura, Norimasa; Horibe, Shuji

    2017-12-01

    Aging is the most prominent risk factor for the development of osteoarthritis (OA), which affects knees and causes major health burdens. Meniscal dysfunction mostly based on degeneration contributes to the development and progression of knee OA. Meniscal degeneration is caused by various extrinsic factors, such as repetitive trauma or leg malalignment, while meniscal aging is considered as internal changes, such as molecular or cellular changes. Little is known about age-related changes in the meniscus. Therefore, this review aimed to summarize and clarify the understanding of the aged meniscus. There are few articles about natural aging in the meniscus, because most reports only demonstrate the effects of OA on the meniscus. We searched PubMed (1948 to November 2016) to identify and summarize all English-language articles evaluating natural aging in the meniscus. There is evidence of compositional change in the meniscus with aging, involving cells, collagens, and proteoglycans. In addition, as recent reports on the natural aging of cartilage have indicated, senescence of the meniscal cells may also lead to disruption of meniscal cells and tissue homeostasis. Due to the low turnover rate of collagen, accumulation of advanced glycation end-products largely contributes to tissue stiffness and vulnerability, and finally results in degenerative changes or tears. Furthermore, environmental factors such as joint fluid secreted by inflamed synovium could also contribute to meniscal tissue deterioration. Age-related changes induce meniscal tissue vulnerability and finally lead to meniscal dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Radiation therapy for age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Takagi, Chikako; Mori, Hideo; Akuta, Keizou [Otsu Red Cross Hospital, Shiga (Japan); Yoshimura, Nagahisa

    1998-04-01

    We evaluated the effect of low-dose radiation on age-related macular degeneration in 8 affected eyes. Radiation was applied using photons at 4 MV. Each eye received 10 fractions of 2 Gy per day over 2 weeks. At 6 months after treatment, funduscopic or angiographic findings had either improved or remained unchanged in all the eyes. The visual acuity improved by 2 lines or more in 2 eyes (25%), remained unchanged in 5 eyes (63%) and deteriorated in 1 eye (13%). At the last examination, fundus findings had improved in 2 eyes (25%), remained unchanged in 1 eye (13%) and deteriorated in 5 eyes (63%). The visual acuity had improved or unchanged in 2 eyes each (25%) and deteriorated in 4 eyes (50%). There has been no negative side effects of radiation. Above findings show that low-dose radiation is potentially beneficial for subfoveal or juxtafoveal choroidal neovascularizations in age-related macular degeneration on a short term basis. (author)

  17. KCNQ channels regulate age-related memory impairment.

    Directory of Open Access Journals (Sweden)

    Sonia Cavaliere

    Full Text Available In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/βneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment.

  18. Age-Related Eye Disease and Participation in Cognitive Activities.

    Science.gov (United States)

    Varin, Melanie; Kergoat, Marie-Jeanne; Belleville, Sylvie; Li, Gisele; Rousseau, Jacqueline; Roy-Gagnon, Marie-Hélène; Moghadaszadeh, Solmaz; Freeman, Ellen E

    2017-12-21

    Studies have found a benefit to living a cognitively active life in older age. Our goal was to quantify participation in cognitively stimulating activities in adults with and without age-related eye disease. We conducted a cross-sectional hospital-based study in Montreal, Canada of older adults (n = 303) having either age-related macular degeneration (AMD) (n = 96), glaucoma (n = 93), or normal vision (n = 114). To be eligible, the AMD group had to have bilateral late stage AMD with a better eye visual acuity of 20/30 or worse. The glaucoma group had to have a diagnosis of bilateral primary open-angle glaucoma with visual field mean deviation Cognitive activities were measured using the Victoria Longitudinal Study Activity Questionnaire. Linear regression was used. Patients with AMD (β = -4.2, 95% confidence interval (CI) -6.0, -2.4) and glaucoma (β = -1.8, 95% CI -3.3, -0.3) participated in fewer cognitive activities per month compared to those with normal vision after adjusting for age, sex, education, diabetes, number of comorbidities, cognition, and cataract. People with AMD and glaucoma participated in fewer cognitive activities, which could put them at risk for future cognitive impairment.

  19. Age-Related Deficits in Reality Monitoring of Action Memories

    Science.gov (United States)

    McDaniel, Mark A.; Lyle, Keith B.; Butler, Karin M.; Dornburg, Courtney C.

    2008-01-01

    We describe three theoretical accounts of age-related increases in falsely remembering that imagined actions were performed (Thomas & Bulevich, 2006). To investigate these accounts and further explore age-related changes in reality monitoring of action memories, we used a new paradigm in which actions were (a) imagined-only (b) actually performed, or (c) both imagined and performed. Older adults were more likely than younger adults to misremember the source of imagined-only actions, with older adults’ more often specifying that the action was imagined and also that it was performed. For both age groups, as repetitions of the imagined-only events increased, illusions that the actions were only performed decreased. These patterns suggest that both older and younger adults utilize qualitative characteristics when making reality-monitoring judgments and that repeated imagination produces richer records of both sensory details and cognitive operations. However, sensory information derived from imagination appears to be more similar to that derived from performance for older than younger adults. PMID:18808253

  20. Age Related Changes in Hematological Values of Myanmar Local Puppies

    Directory of Open Access Journals (Sweden)

    Thandar Oo

    2017-10-01

    Full Text Available The hematological parameters were used to monitor the health status and its components also changed according to the ages. However, there were no reports for this issues in Myanmar local dogs. Thus, this study was carried out to investigate the age-related changes on the hematological parameters of local puppies in Myanmar. Ten local puppies with the age of 2-3 month old were used in this experiment, which was lasted for 8 weeks.The daily clinical examinations were conducted throughout the entire experimental period for general health check-up. Haematological parameters (Total WBC count and its differential counts, and RBC, HCT, MCV, HGB, MCH, MCHC and platelets were measured bi-weekly with Abacus Vet-5 automate haematology analyser. According to the results, the total WBC and eosinophil counts were not significantly different (P>0.05, while lymphocytes, monocytes, neutrophils and basophils were significantly different (P0.05 throughout the experimental periods. Thus, the age-related changes were observed on cell counts of lymphocytes, monocytes, neutrophils, basophils in Myanmar local puppies.

  1. KCNQ channels regulate age-related memory impairment.

    Science.gov (United States)

    Cavaliere, Sonia; Malik, Bilal R; Hodge, James J L

    2013-01-01

    In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ) when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/βneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment.

  2. Age-related retinopathy in NRF2-deficient mice.

    Directory of Open Access Journals (Sweden)

    Zhenyang Zhao

    2011-04-01

    Full Text Available Cumulative oxidative damage is implicated in the pathogenesis of age-related macular degeneration (AMD. Nuclear factor erythroid 2-related factor 2 (NRF2 is a transcription factor that plays key roles in retinal antioxidant and detoxification responses. The purposes of this study were to determine whether NRF2-deficient mice would develop AMD-like retinal pathology with aging and to explore the underlying mechanisms.Eyes of both wild type and Nrf2(-/- mice were examined in vivo by fundus photography and electroretinography (ERG. Structural changes of the outer retina in aged animals were examined by light and electron microscopy, and immunofluorescence labeling. Our results showed that Nrf2(-/- mice developed age-dependent degenerative pathology in the retinal pigment epithelium (RPE. Drusen-like deposits, accumulation of lipofuscin, spontaneous choroidal neovascularization (CNV and sub-RPE deposition of inflammatory proteins were present in Nrf2(-/- mice after 12 months. Accumulation of autophagy-related vacuoles and multivesicular bodies was identified by electron microscopy both within the RPE and in Bruch's membrane of aged Nrf2(-/- mice.Our data suggest that disruption of Nfe2l2 gene increased the vulnerability of outer retina to age-related degeneration. NRF2-deficient mice developed ocular pathology similar to cardinal features of human AMD and deregulated autophagy is likely a mechanistic link between oxidative injury and inflammation. The Nrf2(-/- mice can provide a novel model for mechanistic and translational research on AMD.

  3. The Drosophila melanogaster circadian pacemaker circuit

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... As an experimental model system, the fruit fly Drosophila melanogaster has been seminal in shaping our understanding of the circadian clockwork. The wealth of genetic tools at our disposal over the past four decades has enabled discovery of the genetic and molecular bases of circadian rhythmicity.

  4. The Drosophila melanogaster circadian pacemaker circuit

    Indian Academy of Sciences (India)

    2008-12-07

    Dec 7, 2008 ... system for the study of circadian rhythms primarily due to the availability of molecular genetic tools that enabled iden- tification of genes, proteins and neuronal groups that are es- sential components of the circadian machinery. Further, D. melanogaster exhibits robust and relatively easily measur-.

  5. Radioresistance and radiosensitivity in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Reguly, M.L.

    1983-01-01

    Studying the mechanisms controlling radioresistant in Drosophila the sensibility of four strains of Drosophila melanogaster to sex-linked recessive lethal mutations induced by 5kR Cobalt-60 gamma radiation and 0,006 M EMS or 0,25% of caffeine was determined. (M.A.C.) [pt

  6. Radioresistance and radiosensitivity in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Reguly, M.L.; Marques, E.K.

    1987-01-01

    The mechanisms of radioresistance in Drosophila are studied. The mutagenic effects of 5KR of 60 Cobalt gamma radiation and of 0,006M dose of ethyl methanesulfonate (EMS) on four D. Melanogaster strains (RC 1 , CO 3 , BUE and LEN) are investigated. (M.A.C.) [pt

  7. Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

    DEFF Research Database (Denmark)

    Knecht, Wolfgang; Mikkelsen, N.E.; Clausen, A.R.

    2009-01-01

    Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (Dm-dNK) can additionally sensitize human cancer cell lines towards the anti-cancer drug gemcitabine. We show that this property is based on the Dm-dNK ability to efficiently phosphorylate gemcitabine. The 2.2 angstrom resolution...

  8. Mapping selection within Drosophila melanogaster embryo's anatomy

    DEFF Research Database (Denmark)

    Salvador-Martínez, Irepan; Coronado-Zamora, Marta; Castellano, David

    2018-01-01

    We present a survey of selection across Drosophila melanogaster embryonic anatomy. Our approach integrates genomic variation, spatial gene expression patterns and development, with the aim of mapping adaptation over the entire embryo's anatomy. Our adaptation map is based on analyzing spatial gen...

  9. Intersex (ix) mutations of Drosophila melanogaster cause ...

    Indian Academy of Sciences (India)

    In Drosophila melanogaster, the intersex (ix) is a terminally positioned gene in somatic sex determination hierarchy and function with the female specific product of double sex (DSXF) to implement female sexual differentiation. The null phenotype of ix is to transform diplo-X individuals into intersexes while leaving haplo-X ...

  10. Quantifying Abdominal Pigmentation in Drosophila melanogaster.

    Science.gov (United States)

    Saleh Ziabari, Omid; Shingleton, Alexander W

    2017-06-01

    Pigmentation is a morphologically simple but highly variable trait that often has adaptive significance. It has served extensively as a model for understanding the development and evolution of morphological phenotypes. Abdominal pigmentation in Drosophila melanogaster has been particularly useful, allowing researchers to identify the loci that underlie inter- and intraspecific variations in morphology. Hitherto, however, D. melanogaster abdominal pigmentation has been largely assayed qualitatively, through scoring, rather than quantitatively, which limits the forms of statistical analysis that can be applied to pigmentation data. This work describes a new methodology that allows for the quantification of various aspects of the abdominal pigmentation pattern of adult D. melanogaster. The protocol includes specimen mounting, image capture, data extraction, and analysis. All the software used for image capture and analysis feature macros written for open-source image analysis. The advantage of this approach is the ability to precisely measure pigmentation traits using a methodology that is highly reproducible across different imaging systems. While the technique has been used to measure variation in the tergal pigmentation patterns of adult D. melanogaster, the methodology is flexible and broadly applicable to pigmentation patterns in myriad different organisms.

  11. The Drosophila melanogaster circadian pacemaker circuit

    Indian Academy of Sciences (India)

    More recently, detailed investigation leading to the anatomical, neurochemical and electrophysiological characterization of the various neuronal subgroups that comprise the circadian machinery has revealed pathways through which these neurons come together to act as a neuronal circuit. Thus the D. melanogaster ...

  12. Association of gait and balance disorders with age-related white matter changes: the LADIS study

    DEFF Research Database (Denmark)

    Baezner, H.; Blahak, C.; Poggesi, A.

    2008-01-01

    % CI 1.02 to 2.52; severe vs mild ARWMC: odds ratio 1.75, 95% CI 1.09 to 2.80). CONCLUSIONS: Our findings support a strong association between the severity of age-related white matter changes and the severity of gait and motor compromise. Physical activity might have the potential to reduce the risk......OBJECTIVE: In the Leukoaraiosis and Disability (LADIS) Study, 11 European centers are evaluating the role of age-related white matter changes (ARWMC) as an independent determinant of the transition to disability in the elderly (65 to 84 years). We aimed at determining the influence of ARWMC...... was best in individuals with mild ARWMC (single leg stance time: 18.9 +/- 10.8 seconds) compared with moderate and severe ARWMC (16.4 +/- 10.8 and 13.6 +/- 11.2 seconds) (p pathologic SPPB score (moderate vs mild ARWMC: odds ratio 1.60, 95...

  13. Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration.

    Science.gov (United States)

    Liu, Wenxuan; Klose, Alanna; Forman, Sophie; Paris, Nicole D; Wei-LaPierre, Lan; Cortés-Lopéz, Mariela; Tan, Aidi; Flaherty, Morgan; Miura, Pedro; Dirksen, Robert T; Chakkalakal, Joe V

    2017-06-06

    Neuromuscular junction degeneration is a prominent aspect of sarcopenia, the age-associated loss of skeletal muscle integrity. Previously, we showed that muscle stem cells activate and contribute to mouse neuromuscular junction regeneration in response to denervation (Liu et al., 2015). Here, we examined gene expression profiles and neuromuscular junction integrity in aged mouse muscles, and unexpectedly found limited denervation despite a high level of degenerated neuromuscular junctions. Instead, degenerated neuromuscular junctions were associated with reduced contribution from muscle stem cells. Indeed, muscle stem cell depletion was sufficient to induce neuromuscular junction degeneration at a younger age. Conversely, prevention of muscle stem cell and derived myonuclei loss was associated with attenuation of age-related neuromuscular junction degeneration, muscle atrophy, and the promotion of aged muscle force generation. Our observations demonstrate that deficiencies in muscle stem cell fate and post-synaptic myogenesis provide a cellular basis for age-related neuromuscular junction degeneration and associated skeletal muscle decline.

  14. Combining voxel-based morphometry and diffusion tensor imaging to detect age-related brain changes.

    Science.gov (United States)

    Lehmbeck, Jan T; Brassen, Stefanie; Weber-Fahr, Wolfgang; Braus, Dieter F

    2006-04-03

    The present study combined optimized voxel-based morphometry and diffusion tensor imaging to detect age-related brain changes. We compared grey matter density maps (grey matter voxel-based morphometry) and white matter fractional anisotropy maps (diffusion tensor imaging-voxel-based morphometry) between two groups of 17 younger and 17 older women. Older women exhibited reduced white matter fractional anisotropy as well as decreased grey matter density most prominently in the frontal, limbic, parietal and temporal lobes. A discriminant analysis identified four frontal and limbic grey and white matter areas that separated the two groups most effectively. We conclude that grey matter voxel-based morphometry and diffusion tensor imaging voxel-based morphometry are well suited for the detection of age-related changes and their combination provides high accuracy when detecting the neural correlates of aging.

  15. Transplantation of retinal pigment epithelial cells - a possible future treatment for age-related macular degeneration

    DEFF Research Database (Denmark)

    Wiencke, Anne Katrine

    2001-01-01

    ophthalmology, age-related macular degeneration, retinal pigment epithelial cells, transplantation, treatment......ophthalmology, age-related macular degeneration, retinal pigment epithelial cells, transplantation, treatment...

  16. Transplantation of retinal pigment epithelial cells - a possible future treatment for age-related macular degeneration

    DEFF Research Database (Denmark)

    Wiencke, Anne Katrine

    2001-01-01

    ophthalmology, age-related macular degeneration, transplantation, retinal pigment epithelial cells, treatment......ophthalmology, age-related macular degeneration, transplantation, retinal pigment epithelial cells, treatment...

  17. Prevalence of age-related maculopathy and age-related macular degeneration among the inuit in Greenland. The Greenland Inuit Eye Study

    DEFF Research Database (Denmark)

    Andersen, Mads Varis Nis; Rosenberg, Thomas; la Cour, Morten

    2008-01-01

    To examine the age- and gender-specific prevalence and describe the common phenotype of early age-related maculopathy (ARM) and late-stage age-related macular degeneration (AMD) among the Inuit in Greenland.......To examine the age- and gender-specific prevalence and describe the common phenotype of early age-related maculopathy (ARM) and late-stage age-related macular degeneration (AMD) among the Inuit in Greenland....

  18. Rapid Assessment of Age-Related Differences in Standing Balance

    Directory of Open Access Journals (Sweden)

    Tobias Kalisch

    2011-01-01

    Full Text Available As life expectancy continues to rise, in the future there will be an increasing number of older people prone to falling. Accordingly, there is an urgent need for comprehensive testing of older individuals to collect data and to identify possible risk factors for falling. Here we use a low-cost force platform to rapidly assess deficits in balance under various conditions. We tested 21 healthy older adults and 24 young adults during static stance, unidirectional and rotational displacement of their centre of pressure (COP. We found an age-related increase in postural sway during quiet standing and a reduction of maximal COP displacement in unidirectional and rotational displacement tests. Our data show that even low-cost computerized assessment tools allow for the comprehensive testing of balance performance in older subjects.

  19. Redox control of senescence and age-related disease

    Directory of Open Access Journals (Sweden)

    Akshaya Chandrasekaran

    2017-04-01

    Full Text Available The signaling networks that drive the aging process, associated functional deterioration, and pathologies has captured the scientific community's attention for decades. While many theories exist to explain the aging process, the production of reactive oxygen species (ROS provides a signaling link between engagement of cellular senescence and several age-associated pathologies. Cellular senescence has evolved to restrict tumor progression but the accompanying senescence-associated secretory phenotype (SASP promotes pathogenic pathways. Here, we review known biological theories of aging and how ROS mechanistically control senescence and the aging process. We also describe the redox-regulated signaling networks controlling the SASP and its important role in driving age-related diseases. Finally, we discuss progress in designing therapeutic strategies that manipulate the cellular redox environment to restrict age-associated pathology.

  20. Imaging geographic atrophy in age-related macular degeneration.

    Science.gov (United States)

    Göbel, Arno P; Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Brinkmann, Christian K; Holz, Frank G

    2011-01-01

    Advances in retinal imaging technology have largely contributed to the understanding of the natural history, prognostic markers and disease mechanisms of geographic atrophy (GA) due to age-related macular degeneration. There is still no therapy available to halt or slow the disease process. In order to evaluate potential therapeutic effects in interventional trials, there is a need for precise quantification of the GA progression rate. Fundus autofluorescence imaging allows for accurate identification and segmentation of atrophic areas and currently represents the gold standard for evaluating progressive GA enlargement. By means of high-resolution spectral-domain optical coherence tomography, distinct microstructural alterations related to GA can be visualized. Copyright © 2011 S. Karger AG, Basel.

  1. [Future methods of treatment in age related macular degeneration].

    Science.gov (United States)

    Turlea, C

    2012-01-01

    In the present time the treatment of Age Related Macular Degeneration (ARMD) begins to develop. Many medical therapies are presently tested in the two types of ARMD, geographic atrophy and exudative ARMD. In atrophic ARMD, new drugs are aimed to spare photoreceptors and the retinal pigment epithelium, to prevent oxidative damage on the retina and to suppress the inflammation process. In exudative ARMD, new therapies are already in use and in progress, especially the anti-VEGF factors, and others try to improve visual prognosis in targeting other mechanism or cells involved in the angiogenesis process. This article reviews and summarizes the available data, presented in several scientific meetings, congresses or given directly by the companies involved.

  2. Age-related macular degeneration: epidemiology and optimal treatment

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    cause of blindness among Caucasian individuals in developed countries. Blindness resulting from AMD rarely occurs before age 70, and most cases occur after age 80. The age-standardised 1-year incidence of legal blindness resulting from AMD is 212 cases per million. Two-thirds of AMD cases have CNV......Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian...... individuals than in pigmented races. In predominantly Caucasian populations, the age-standardised prevalence of AMD in at least one eye is 7760 cases per million. The age-standardised cumulated 1-year incidence of AMD in at least one eye is 1051 cases per million individuals. AMD is the most important single...

  3. Cognitive dysfunction and age-related macular degeneration.

    Science.gov (United States)

    Rozzini, Luca; Riva, Maddalena; Ghilardi, Nausica; Facchinetti, Paola; Forbice, Eliana; Semeraro, Francesco; Padovani, Alessandro

    2014-05-01

    Several previous studies showed that age-related macular degeneration (AMD) and Alzheimer's disease (AD) share common risk factors and histopathology changes, and there is epidemiological evidence linking AMD to cognitive impairment. We tested this theory in 51 patients with late-stage AMD and 24 controls by analyzing their neuropsychological profiles. In this study, data showed that patients affected by late-stage AMD have a worse global cognitive function than those of the controls and, in particular, show worse performances in memory tasks. Moreover, patients affected by the dry form of AMD are significantly impaired in executive functions in addition to memory. Data support the hypothesis of a possible association between AMD and cognitive impairment. In particular, patients affected by the dry form of AMD may be at greater risk of developing subsequent dementia.

  4. Risk Factors and Biomarkers of Age-Related Macular Degeneration

    Science.gov (United States)

    Lambert, Nathan G.; Singh, Malkit K.; ElShelmani, Hanan; Mansergh, Fiona C.; Wride, Michael A.; Padilla, Maximilian; Keegan, David; Hogg, Ruth E.; Ambati, Balamurali K.

    2016-01-01

    A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence, identify at risk individuals, elucidate causative pathophysiological etiologies, guide screening, monitoring and treatment parameters, and predict disease outcomes. To date, a host of genetic, environmental, proteomic, and cellular targets have been identified as both risk factors and potential biomarkers for AMD. Despite this, their use has been confined to research settings and has not yet crossed into the clinical arena. A greater understanding of these factors and their use as potential biomarkers for AMD can guide future research and clinical practice. This article will discuss known risk factors and novel, potential biomarkers of AMD in addition to their application in both academic and clinical settings. PMID:27156982

  5. Vitamin D and Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Alfredo Garcia Layana

    2017-10-01

    Full Text Available In recent years, the relationship between vitamin D and health has received growing attention from the scientific and medical communities. Vitamin D deficiencies have been repeatedly associated with various acute and chronic diseases, including age-related macular degeneration (AMD. Its active metabolite, 1α,25-dihydoxy vitamin D, acts as a modulator of cell proliferation, differentiation and apoptosis, and cumulative data from experimental and observational studies suggest that relatively a lower vitamin D status could be a potential risk factor for the development of early and/or late AMD. Herein, we made a narrative review of the mechanisms linking a potential role of vitamin D with the current concepts of AMD pathophysiology.

  6. Redox control of senescence and age-related disease.

    Science.gov (United States)

    Chandrasekaran, Akshaya; Idelchik, Maria Del Pilar Sosa; Melendez, J Andrés

    2017-04-01

    The signaling networks that drive the aging process, associated functional deterioration, and pathologies has captured the scientific community's attention for decades. While many theories exist to explain the aging process, the production of reactive oxygen species (ROS) provides a signaling link between engagement of cellular senescence and several age-associated pathologies. Cellular senescence has evolved to restrict tumor progression but the accompanying senescence-associated secretory phenotype (SASP) promotes pathogenic pathways. Here, we review known biological theories of aging and how ROS mechanistically control senescence and the aging process. We also describe the redox-regulated signaling networks controlling the SASP and its important role in driving age-related diseases. Finally, we discuss progress in designing therapeutic strategies that manipulate the cellular redox environment to restrict age-associated pathology. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Age-related decline in global form suppression

    DEFF Research Database (Denmark)

    Wiegand, Iris Michaela; Finke, Kathrin; Töllner, Thomas

    2015-01-01

    differences in the subsequent (250–500 ms) posterior contralateral negativity (PCN) indicated that attentional resources were allocated faster to Kanisza, as compared to non-Kanisza, targets in both age groups, while the allocation of spatial attention seemed to be generally delayed in older relative...... to younger age. Our results suggest that the enhanced global-local asymmetry in the older age group originated from less effective suppression of global distracter forms on early processing stages – indicative of older observers having difficulties with disengaging from a global default selection mode....... Selective attention, i.e., the ability to focus on relevant and ignore irrelevant information, declines with increasing age; however, how this deficit affects selection of global vs. local configurations remains unknown. On this background, the present study examined for age-related differences in a global...

  8. Age-related differences in multiple task monitoring.

    Directory of Open Access Journals (Sweden)

    Ivo Todorov

    Full Text Available Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age.

  9. Age-related differences in multiple task monitoring.

    Science.gov (United States)

    Todorov, Ivo; Del Missier, Fabio; Mäntylä, Timo

    2014-01-01

    Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age.

  10. Age-related changes in contextual associative learning.

    Science.gov (United States)

    Luu, Trinh T; Pirogovsky, Eva; Gilbert, Paul E

    2008-01-01

    The hippocampus plays a critical role in processing contextual information. Although age-related changes in the hippocampus are well documented in humans, nonhuman primates, and rodents, few studies have examined contextual learning deficits in old rats. The present study investigated age-related differences in contextual associative learning in young (6 mo) and old (24 mo) rats using olfactory stimuli. Stimuli consisted of common odors mixed in sand and placed in clear plastic cups. Testing was conducted in two boxes that represented two different contexts (Context 1 and Context 2). The contexts varied based on environmental features of the box such as color (black vs. white), visual cues on the walls of the box, and flooring texture. Each rat was simultaneously presented with two cups, one filled with Odor A and one filled with Odor B in each context. In Context 1, the rat received a food reward for digging in the cup containing Odor A, but did not receive a food reward for digging in the cup containing Odor B. In Context 2, the rat was rewarded for digging in the cup containing Odor B, but did receive a reward for digging in the cup containing Odor A. Therefore, the rat learned to associate Context 1 with Odor A and Context 2 with Odor B. The rat was tested for eight days using the same odor problem throughout all days of testing. The results showed no significant difference between young and old rats on the first two days of testing; however, young rats significantly outperformed old rats on Day 3. Young rats continued to maintain superior performance compared to old rats on Days 4-8. The results suggest that aging results in functional impairments in brain regions that support memory for associations between specific cues and their respective context.

  11. Age-related changes in the retinal pigment epithelium (RPE.

    Directory of Open Access Journals (Sweden)

    Xiaorong Gu

    Full Text Available Age-related changes in the retina are often accompanied by visual impairment but their mechanistic details remain poorly understood.Proteomic studies were pursued toward a better molecular understanding of retinal pigment epithelium (RPE aging mechanisms. RPE cells were isolated from young adults (3-4 month-old and old (24-25 month-old F344BN rats, and separated into subcellular fractions containing apical microvilli (MV and RPE cell bodies (CB lacking their apical microvilli. Proteins were extracted in detergent, separated by SDS-PAGE, digested in situ with trypsin and analyzed by LC MS/MS. Select proteins detected in young and old rat RPE were further studied using immunofluorescence and Western blot analysis.A total of 356 proteins were identified in RPE MV from young and 378 in RPE MV from old rats, 48% of which were common to each age group. A total of 897 proteins were identified in RPE CB from young rats and 675 in old CB, 56% of which were common to each age group. Several of the identified proteins, including proteins involved in response to oxidative stress, displayed both quantitative and qualitative changes in overall abundance during RPE aging. Numerous proteins were identified for the first time in the RPE. One such protein, collectrin, was localized to the apical membrane of apical brush border of proximal tubules where it likely regulates several amino acid transporters. Elsewhere, collectrin is involved in pancreatic β cell proliferation and insulin secretion. In the RPE, collectrin expression was significantly modulated during RPE aging. Another age-regulated, newly described protein was DJ-1, a protein extensively studied in brain where oxidative stress-related functions have been described.The data presented here reveals specific changes in the RPE during aging, providing the first protein database of RPE aging, which will facilitate future studies of age-related retinal diseases.

  12. Age-related degradation of Westinghouse 480-volt circuit breakers

    International Nuclear Information System (INIS)

    Subudhi, M.; MacDougall, E.; Kochis, S.; Wilhelm, W.; Lee, B.S.

    1990-11-01

    After the McGuire event in 1987 relating to failure of the center pole weld in one of its reactor trip breakers, activities were initiated by the NRC to investigate the probable causes. A review of operating experience suggested that the burning of coils, jamming of the operating mechanism, and deterioration of the contacts dominated the breakers failures. Although failures of the pole shaft weld were not included as one of the generic problems, the NRC augmented inspection team had suspected that these welds were substandard which led them to crack prematurely. A DS-416 low voltage air circuit breaker manufactured by Westinghouse was mechanically cycled to identify age-related degradations. This accelerated aging test was conducted for over 36,000 cycles during nine months. Three separate pole shafts, one with a 60 degree weld, one with a 120 degree and one with a 180 degree were used to characterize the cracking in the pole level welds. In addition, three different operating mechanisms and several other parts were replaced as they became inoperable. The testing yielded many useful results. The burning of the closing coils was found to be the effect of binding in the linkages that are connected to this device. Among the seven welds on the pole shaft, number-sign 1 and number-sign 3 were the critical ones which cracked first to cause misalignment of the pole levers, which, in turn, had led to many problems with the operating mechanism including the burning of coils, excessive wear in certain parts, and overstressed linkages. Based on these findings, a maintenance program is suggested to alleviate the age-related degradations that occur due to mechanical cycling of this type of breaker. 3 refs., 39 figs., 7 tabs

  13. Monoamine oxidase enzymes and oxidative stress in the rat optic nerve: age-related changes.

    Science.gov (United States)

    Nebbioso, Marcella; Pascarella, Antonia; Cavallotti, Carlo; Pescosolido, Nicola

    2012-12-01

    In this study, age-related changes in the monoamine oxidases (MAO) were studied in the optic nerve (ON) of both young and aged male rats. The aim of the study was to assess the role of MAO in age-related changes in the rat ON and explain the mechanisms of neuroprotection mediated by MAO-B-specific inhibitors. Fifteen three month old and fifteen 26 month old Sprague-Dawley rats were used. The animals were killed by terminal anaesthesia. Staining of MAO, quantitative analysis of images, biochemical assays and statistical analysis of data were carried out. Samples of the ON were washed in water, fixed in Bowen fluid, dehydrated and embedded in Entellan. Histological sections were stained for MAO-enzymatic activities. The specificity of the reaction was evaluated by incubating control sections in a medium either without substrate or without dye. The quantitative analysis of images was carried out at the same magnification and the same lighting using a Zeiss photomicroscope. The histochemical findings were compared with the biochemical results. After enzymatic staining, MAO could be demonstrated in the ON fibres of both young and aged animals; however, MAO were increased in the nerve fibres of the elderly rats. These morphological findings were confirmed biochemically. The possibility that age-related changes in MAO levels may be attributed to impaired energy production mechanisms and/or represent the consequence of reduced energy needs is discussed. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.

  14. Stereotactic radiotherapy for wet age-related macular degeneration: current perspectives

    Directory of Open Access Journals (Sweden)

    Neffendorf JE

    2015-09-01

    Full Text Available James E Neffendorf, Timothy L Jackson Department of Ophthalmology, School of Medicine, King’s College London, London, United Kingdom Abstract: Neovascular age-related macular degeneration is a leading cause of blindness in the developed world. Currently, the treatment of choice is intravitreal injections of anti-VEGF medications. These require frequent dosing, up to monthly, and impose a substantial burden on patients and the health economy. Ionizing radiation was proposed as a possible treatment for age-related macular degeneration due to its anti-inflammatory and anti-fibrotic properties. Stereotactic radiotherapy is an outpatient-based radiotherapy platform that provides stereotactic application of low energy X-ray to the retina in three highly collimated beams that cross the inferior sclera to overlap at the macula. A randomized, double-masked, sham-controlled trial of 230 patients (INTREPID showed that a single dose of stereotactic radiotherapy significantly reduces the number of intravitreal anti-VEGF injections needed over 2 years. A larger randomized controlled trial (STAR is underway. Keywords: wet age-related macular degeneration, radiation therapy, stereotactic radiotherapy, vascular endothelial growth factor

  15. Gadd45 proteins: relevance to aging, longevity and age-related pathologies.

    Science.gov (United States)

    Moskalev, Alexey A; Smit-McBride, Zeljka; Shaposhnikov, Mikhail V; Plyusnina, Ekaterina N; Zhavoronkov, Alex; Budovsky, Arie; Tacutu, Robi; Fraifeld, Vadim E

    2012-01-01

    The Gadd45 proteins have been intensively studied, in view of their important role in key cellular processes. Indeed, the Gadd45 proteins stand at the crossroad of the cell fates by controlling the balance between cell (DNA) repair, eliminating (apoptosis) or preventing the expansion of potentially dangerous cells (cell cycle arrest, cellular senescence), and maintaining the stem cell pool. However, the biogerontological aspects have not thus far received sufficient attention. Here we analyzed the pathways and modes of action by which Gadd45 members are involved in aging, longevity and age-related diseases. Because of their pleiotropic action, a decreased inducibility of Gadd45 members may have far-reaching consequences including genome instability, accumulation of DNA damage, and disorders in cellular homeostasis - all of which may eventually contribute to the aging process and age-related disorders (promotion of tumorigenesis, immune disorders, insulin resistance and reduced responsiveness to stress). Most recently, the dGadd45 gene has been identified as a longevity regulator in Drosophila. Although further wide-scale research is warranted, it is becoming increasingly clear that Gadd45s are highly relevant to aging, age-related diseases (ARDs) and to the control of life span, suggesting them as potential therapeutic targets in ARDs and pro-longevity interventions. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. The Marmoset as a Model of Aging and Age-Related Diseases

    Science.gov (United States)

    Tardif, Suzette D.; Mansfield, Keith G.; Ratnam, Rama; Ross, Corinna N.; Ziegler, Toni E.

    2013-01-01

    The common marmoset (Callithrix jacchus) is poised to become a standard nonhuman primate aging model. With an average lifespan of 5 to 7 years and a maximum lifespan of 16.5 years, marmosets are the shortest-lived anthropoid primates. They display age-related changes in pathologies that mirror those seen in humans, such as cancer, amyloidosis, diabetes, and chronic renal disease. They also display predictable age-related differences in lean mass, calf circumference, circulating albumin, hemoglobin, and hematocrit. Features of spontaneous sensory and neurodegenerative change—for example, reduced neurogenesis, β-amyloid deposition in the cerebral cortex, loss of calbindin D28k binding, and evidence of presbycusis—appear between the ages of 7 and 10 years. Variation among colonies in the age at which neurodegenerative change occurs suggests the interesting possibility that marmosets could be specifically managed to produce earlier versus later occurrence of degenerative conditions associated with differing rates of damage accumulation. In addition to the established value of the marmoset as a model of age-related neurodegenerative change, this primate can serve as a model of the integrated effects of aging and obesity on metabolic dysfunction, as it displays evidence of such dysfunction associated with high body weight as early as 6 to 8 years of age. PMID:21411858

  17. Sleep Duration and Age-Related Changes in Brain Structure and Cognitive Performance

    Science.gov (United States)

    Lo, June C.; Loh, Kep Kee; Zheng, Hui; Sim, Sam K.Y.; Chee, Michael W.L.

    2014-01-01

    Study Objectives: To investigate the contribution of sleep duration and quality to age-related changes in brain structure and cognitive performance in relatively healthy older adults. Design: Community-based longitudinal brain and cognitive aging study using a convenience sample. Setting: Participants were studied in a research laboratory. Participants: Relatively healthy adults aged 55 y and older at study commencement. Interventions: N/A. Measurements and Results: Participants underwent magnetic resonance imaging and neuropsychological assessment every 2 y. Subjective assessments of sleep duration and quality and blood samples were obtained. Each hour of reduced sleep duration at baseline augmented the annual expansion rate of the ventricles by 0.59% (P = 0.007) and the annual decline rate in global cognitive performance by 0.67% (P = 0.050) in the subsequent 2 y after controlling for the effects of age, sex, education, and body mass index. In contrast, global sleep quality at baseline did not modulate either brain or cognitive aging. High-sensitivity C-reactive protein, a marker of systemic inflammation, showed no correlation with baseline sleep duration, brain structure, or cognitive performance. Conclusions: In healthy older adults, short sleep duration is associated with greater age-related brain atrophy and cognitive decline. These associations are not associated with elevated inflammatory responses among short sleepers. Citation: Lo JC, Loh KK, Zheng H, Sim SK, Chee MW. Sleep duration and age-related changes in brain structure and cognitive performance. SLEEP 2014;37(7):1171-1178. PMID:25061245

  18. Evaluation of an oral telomerase activator for early age-related macular degeneration - a pilot study.

    Science.gov (United States)

    Dow, Coad Thomas; Harley, Calvin B

    2016-01-01

    Telomere attrition and corresponding cellular senescence of the retinal pigment epithelium contribute to the changes of age-related macular degeneration. Activation of the enzyme telomerase can add telomeric DNA to retinal pigment epithelium chromosomal ends and has been proposed as a treatment for age-related macular degeneration. We report the use of a small molecule, oral telomerase activator (TA)-65 in early macular degeneration. This study, focusing on early macular degeneration, provides a model for the use of TAs in age-related disease. Thirty-eight (38) patients were randomly assigned to a 1-year, double-blinded, placebo-controlled interventional study with arms for oral TA-65 or placebo. Macular functions via micro-perimetry were the primary measured outcomes. The macular function in the arm receiving the TA-65 showed significant improvement relative to the placebo control. The improvement was manifest at 6 months and was maintained at 1 year: macular threshold sensitivity (measured as average dB [logarithmic decibel scale of light attenuation]) improved 0.97 dB compared to placebo (P-value 0.02) and percent reduced thresholds lessened 8.2% compared to the placebo arm (P-value 0.04). The oral TA significantly improved the macular function of treatment subjects compared to controls. Although this study was a pilot and a larger study is being planned, it is noteworthy in that it is, to our knowledge, the first randomized placebo-controlled study of a TA supplement.

  19. The role of hippocampal iron concentration and hippocampal volume in age-related differences in memory.

    Science.gov (United States)

    Rodrigue, Karen M; Daugherty, Ana M; Haacke, E Mark; Raz, Naftali

    2013-07-01

    The goal of this study was to examine the relationships between 2 age-sensitive indices of brain integrity--volume and iron concentration--and the associated age differences in memory performance. In 113 healthy adults (age 19-83 years), we measured the volume and estimated iron concentration in the hippocampus (HC), caudate nucleus (Cd), and primary visual cortex (VC) in vivo with T2* relaxation times, and assessed memory performance with multiple tests. We applied structural equation modeling to evaluate the contribution of individual differences in 2 indices of integrity, volume and T2*, to age-related memory variance. The results show that in healthy adults, age differences in memory can be explained in part by individual differences in HC volume that in turn are associated with differences in HC iron concentration. Lower memory scores were linked to smaller HC and higher HC iron concentration. No such associations were noted for Cd and VC. We conclude that the association between age-related declines in memory and reduced hippocampal volume may reflect the impact of oxidative stress related to increase in free iron concentration. Longitudinal follow-up is needed to test whether altered iron homeostasis in the HC is an early marker for age-related cognitive decline.

  20. Reduced larval feeding rate is a strong evolutionary correlate of ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 85; Issue 3. Reduced larval feeding rate is a strong evolutionary correlate of rapid development in Drosophila melanogaster. M. Rajamani N. Raghavendra ... Keywords. life-history evolution; development time; larval feeding rate; competition; tradeoffs; Drosophila melanogaster.

  1. The translation factors of Drosophila melanogaster.

    Science.gov (United States)

    Marygold, Steven J; Attrill, Helen; Lasko, Paul

    2017-01-02

    Synthesis of polypeptides from mRNA (translation) is a fundamental cellular process that is coordinated and catalyzed by a set of canonical 'translation factors'. Surprisingly, the translation factors of Drosophila melanogaster have not yet been systematically identified, leading to inconsistencies in their nomenclature and shortcomings in functional (Gene Ontology, GO) annotations. Here, we describe the complete set of translation factors in D. melanogaster, applying nomenclature already in widespread use in other species, and revising their functional annotation. The collection comprises 43 initiation factors, 12 elongation factors, 3 release factors and 6 recycling factors, totaling 64 of which 55 are cytoplasmic and 9 are mitochondrial. We also provide an overview of notable findings and particular insights derived from Drosophila about these factors. This catalog, together with the incorporation of the improved nomenclature and GO annotation into FlyBase, will greatly facilitate access to information about the functional roles of these important proteins.

  2. The age-related positivity effect in electronic gambling.

    Science.gov (United States)

    Bailey, Phoebe E; Gonsalvez, Craig J; Maiuolo, Michelle; Leon, Tarren; Benedek, Gülten

    2018-01-01

    Older adults are increasingly spending time and money playing electronic gambling machines (EGMs). The current study assessed whether the age-related positivity effect influences responding to various EGM outcomes, including wins and losses of equivalent magnitude and frequency. We also explored cognitive mechanisms potentially underpinning the positivity effect. We recorded the skin conductance response (SCR) of healthy older and younger adults while they played for wins, losses, and fake wins (losses disguised as wins). After every win and fake win, participants were forced to choose red or black to either double their win or lose it. They also provided ratings of enjoyment and excitement, estimated number of wins and losses, and completed measures of cognitive function. Young and older adults demonstrated larger SCRs to wins relative to losses. When these wins and losses were of equivalent magnitude and frequency following a double-or-nothing scenario, only older adults responded more to a win than a loss. There were no age group differences in excitement and enjoyment, but older adults were more accurate than young adults in their recall of wins and losses. During EGM play, young and older adults demonstrate similar patterns on autonomic arousal. However, young adults' responding suggests generalized excitement, whereas older adults respond more to the prospect of financial gain.

  3. [Risk factors for age-related macular degeneration].

    Science.gov (United States)

    Starzycka, M; Słomska, J; Górniak-Bednarz, A; Ortyl, E

    1997-01-01

    To present the results of examinations of the risk factors for age-related macular degeneration (AMD) carried out in the last 3 years. Our clinical material comprised 119 patients, 69 women and 50 men, aged 43-85, mean age 70 years. Using classification according to the worse eye, there were 20 patients with drusen, 27 with atrophic changes and 72 with exudative form and AMD. The following risk factors were evaluated: age, sex, body mass index, history of general medical conditions, cigarette smoking, sun exposure, family history of AMD and ocular conditions such as iris color, lens opacities, hyperopia, gerontoxon and changes in retinal vessels. The significant relationships were found between the development of AMD and the age of patients, as well as between the advanced forms of AMD and the history of cardiovascular diseases and sclerotic changes in retinal vessels, 87% of examined patients have light iris and 52% body mass index above 26. The studies confirmed the role of age in the development of AMD and indicated cardiovascular disturbances, increased body mass index and light iris as the possible risk factors for AMD that are most worth further studying. The special attention should be also paid to drusen as the risk factor of AMD.

  4. Bioactive Nutrients and Nutrigenomics in Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Tania Rescigno

    2017-01-01

    Full Text Available The increased life expectancy and the expansion of the elderly population are stimulating research into aging. Aging may be viewed as a multifactorial process that results from the interaction of genetic and environmental factors, which include lifestyle. Human molecular processes are influenced by physiological pathways as well as exogenous factors, which include the diet. Dietary components have substantive effects on metabolic health; for instance, bioactive molecules capable of selectively modulating specific metabolic pathways affect the development/progression of cardiovascular and neoplastic disease. As bioactive nutrients are increasingly identified, their clinical and molecular chemopreventive effects are being characterized and systematic analyses encompassing the “omics” technologies (transcriptomics, proteomics and metabolomics are being conducted to explore their action. The evolving field of molecular pathological epidemiology has unique strength to investigate the effects of dietary and lifestyle exposure on clinical outcomes. The mounting body of knowledge regarding diet-related health status and disease risk is expected to lead in the near future to the development of improved diagnostic procedures and therapeutic strategies targeting processes relevant to nutrition. The state of the art of aging and nutrigenomics research and the molecular mechanisms underlying the beneficial effects of bioactive nutrients on the main aging-related disorders are reviewed herein.

  5. Age-related neuroinflammatory changes negatively impact on neuronal function

    Directory of Open Access Journals (Sweden)

    Marina A Lynch

    2010-01-01

    Full Text Available Neuroinflammatory changes, characterized by an increase in microglial activation and often accompanied by upregulation of inflammatory cytokines like interleukin-1β (IL-1β, are common to many, if not all, neurodegenerative diseases. Similar, though less dramatic neuroinflammatory changes are also known to occur with age. Among the consequences of these changes is an impairment in synaptic function and the evidence suggests that inflammatory cytokines may be the primary contributory factor responsible for the deficits in synaptic plasticity which have been identified in aged rodents. Specifically a decrease in the ability of aged rats to sustain long-term potentiation (LTP in perforant path-granule cells of the hippocampus is associated with increased microglial activation. This review considers the evidence which suggests a causal relationship between these changes and the factors which contribute to the age-related microglial activation, and reflects on data which demonstrate that agents which inhibit microglial activation also improve ability of rats to sustain LTP.

  6. Ocular Surface Temperature in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Andrea Sodi

    2014-01-01

    Full Text Available Background. The aim of this study is to investigate the ocular thermographic profiles in age-related macular degeneration (AMD eyes and age-matched controls to detect possible hemodynamic abnormalities, which could be involved in the pathogenesis of the disease. Methods. 32 eyes with early AMD, 37 eyes with atrophic AMD, 30 eyes affected by untreated neovascular AMD, and 43 eyes with fibrotic AMD were included. The control group consisted of 44 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, diabetes mellitus, and a body temperature higher than 37.5°C. A total of 186 eyes without pupil dilation were investigated by infrared thermography (FLIR A320. The ocular surface temperature (OST of three ocular points was calculated by means of an image processing technique from the infrared images. Two-sample t-test and one-way analysis of variance (ANOVA test were used for statistical analyses. Results. ANOVA analyses showed no significant differences among AMD groups (P value >0.272. OST in AMD patients was significantly lower than in controls (P>0.05. Conclusions. Considering the possible relationship between ocular blood flow and OST, these findings might support the central role of ischemia in the pathogenesis of AMD.

  7. Age related changes in steroid receptors on cultured lung fibroblasts

    International Nuclear Information System (INIS)

    Barile, F.A.; Bienkowski, R.S.

    1986-01-01

    The number of high affinity glucocorticoid receptors (Ro) on human fetal lung fibroblasts decreases as the cells age in vitro, and it has been suggested that these cell systems may be useful models of age-related changes in vivo. They examined the relation between change in Ro with in vitro aging and donor age. Confluent monolayers of lung fibroblasts at various population doubling levels (PDL), were incubated with ( 3 H)-dexamethasone (( 3 H)Dex) either alone or with excess (.01 mM) Dex. Specific binding was calculated as the difference between radioactivity in cells incubated with and without unlabeled Dex; Scatchard plots were used to analyze the data. Ro, measured as fmol ( 3 H)Dex/10 6 cells, for two lines of human fetal cells (HFL-1 and MRC-5) decreased with increasing age in vitro. However, human newborn (CRL-1485) and adult (CCL-201) cells and fetal rabbit cells (FAB-290), showed increases in Ro with continuous passage. For each cell line, the affinity constant (K/sub d/) did not change significantly with passage. They conclude that the direction of changes in steroid receptor levels on cells aging in vitro is influenced by donor age and species. Caution should be used in applying results obtained from model systems to aging organisms

  8. Proinflammatory cytokines, aging, and age-related diseases.

    Science.gov (United States)

    Michaud, Martin; Balardy, Laurent; Moulis, Guillaume; Gaudin, Clement; Peyrot, Caroline; Vellas, Bruno; Cesari, Matteo; Nourhashemi, Fati

    2013-12-01

    Inflammation is a physiological process that repairs tissues in response to endogenous or exogenous aggressions. Nevertheless, a chronic state of inflammation may have detrimental consequences. Aging is associated with increased levels of circulating cytokines and proinflammatory markers. Aged-related changes in the immune system, known as immunosenescence, and increased secretion of cytokines by adipose tissue, represent the major causes of chronic inflammation. This phenomenon is known as "inflamm-aging." High levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α, and C-reactive protein are associated in the older subject with increased risk of morbidity and mortality. In particular, cohort studies have indicated TNF-α and IL-6 levels as markers of frailty. The low-grade inflammation characterizing the aging process notably concurs at the pathophysiological mechanisms underlying sarcopenia. In addition, proinflammatory cytokines (through a variety of mechanisms, such as platelet activation and endothelial activation) may play a major role in the risk of cardiovascular events. Dysregulation of the inflammatory pathway may also affect the central nervous system and be involved in the pathophysiological mechanisms of neurodegenerative disorders (eg, Alzheimer disease).The aim of the present review was to summarize different targets of the activity of proinflammatory cytokines implicated in the risk of pathological aging. Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

  9. Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG).

    Science.gov (United States)

    Kovacs, Gabor G; Xie, Sharon X; Lee, Edward B; Robinson, John L; Caswell, Carrie; Irwin, David J; Toledo, Jon B; Johnson, Victoria E; Smith, Douglas H; Alafuzoff, Irina; Attems, Johannes; Bencze, Janos; Bieniek, Kevin F; Bigio, Eileen H; Bodi, Istvan; Budka, Herbert; Dickson, Dennis W; Dugger, Brittany N; Duyckaerts, Charles; Ferrer, Isidro; Forrest, Shelley L; Gelpi, Ellen; Gentleman, Stephen M; Giaccone, Giorgio; Grinberg, Lea T; Halliday, Glenda M; Hatanpaa, Kimmo J; Hof, Patrick R; Hofer, Monika; Hortobágyi, Tibor; Ironside, James W; King, Andrew; Kofler, Julia; Kövari, Enikö; Kril, Jillian J; Love, Seth; Mackenzie, Ian R; Mao, Qinwen; Matej, Radoslav; McLean, Catriona; Munoz, David G; Murray, Melissa E; Neltner, Janna; Nelson, Peter T; Ritchie, Diane; Rodriguez, Roberta D; Rohan, Zdenek; Rozemuller, Annemieke; Sakai, Kenji; Schultz, Christian; Seilhean, Danielle; Smith, Vanessa; Tacik, Pawel; Takahashi, Hitoshi; Takao, Masaki; Rudolf Thal, Dietmar; Weis, Serge; Wharton, Stephen B; White, Charles L; Woulfe, John M; Yamada, Masahito; Trojanowski, John Q

    2017-07-01

    Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was >60% with a kappa value of 0.55 (95% CI 0.433-0.645). Moderate agreement (>90%, kappa 0.48, 95% CI 0.457-0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37-0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341-0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534-0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  10. Mechanism of Inflammation in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Francesco Parmeggiani

    2012-01-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

  11. Radiation therapy for age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Ayako; Honda, Kaoru; Ishibashi, Tatsuro; Shioyama, Yoshiyuki [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1998-11-01

    We evaluated the effects of low-dose radiation on choroidal neovascular membrane (CNV) in age-related macular degeneration (AMD). Since Chakravarthy reported the benefits from administration of low-dose external-beam irradiation for CNV, many studies have demonstrated that irradiation could have a beneficial treatment effect, whereas several reports have not. In our hospital, 12 eyes with AMD received 10 Gy of 4 MV photons and the other 9 eyes received 20 Gy. Another 4 eyes were untreated as control. After 6 months of treatment, visual acuity was maintained in 11 eyes, improved in 5 eyes, and deteriorated in 5 eyes of treated patients. In control group, visual acuity was maintained in 1 eye and deteriorated in 3 eyes. The size of CNV regressed in 10 eyes, remained stationary in 2 eyes and progressed in 2 eyes of treated patients, while in control group CNV regressed in 2 eyes and remained stationary in 1 eye. After 12 months some CNV progressed. Although the present result seems to be better than those in previous reports, whether or not the treatment is beneficial has to be awaited. (author)

  12. Age-related cerebral white matter changes on computed tomography

    International Nuclear Information System (INIS)

    Fukuda, Hitoshi; Kobayashi, Shotai; Koide, Hiromi; Yamaguchi, Shuhei; Okada, Kazunori; Shimote, Kouichi; Tsunematsu, Tokugoro

    1989-01-01

    Changes of cerebral white matter on computed cranial tomography related to aging were studied in 70 subjects aged 30 to 94 years. The subjects had no histories of cerebrovascular accidents and no abnormalities in the central nervous system were shown by physical examinations and CT scans. We measured the average attenuation values (CT numbers) of each elliptical region (165 pixels, 0.39cm 2 ) in the bilateral thalamus and twelve areas of deep white matter. Multiple regression analysis was used to assess the effects of age, cranial size and cranial bone CT numbers on the brain CT numbers. We also studied the association between brain CT numbers and brain atrophy, hypertension, diabetes mellitus. CT numbers of frontal white matter surrounding anterior horns decreased with aging in 70 subjects aged 30 to 94 years. No significant correlation between age and brain CT numbers was found in any other region by multivariate analysis, because of the prominent effect of cranial bone CT numbers on brain CT numbers. Although no age-related changes of white matter CT numbers was found in 41 subjects aged 30 to 65 years, there were significant negative correlations between age and white matter CT numbers at all regions in 29 subjects aged 66 to 94 years. Brain atrophy was associated with brain CT numbers. No association was found for hypertension or diabetes mellitus. Brain CT numbers decreased with aging even in neurologically healthy persons in older age. Brain CT numbers also decreased as cerebral atrophy advanced. (author)

  13. The theory behind the age-related positivity effect

    Directory of Open Access Journals (Sweden)

    Andrew E Reed

    2012-09-01

    Full Text Available The positivity effect refers to an age-related trend that favors positive over negative stimuli in cognitive processing. Relative to their younger counterparts, older people attend to and remember more positive than negative information. Since the effect was initially identified and the conceptual basis articulated (Mather & Carstensen, 2005 scores of independent replications and related findings have appeared in the literature. Over the same period, a number of investigations have failed to observe age differences in the cognitive processing of emotional material. When findings are considered in theoretical context, a reliable pattern of evidence emerges that helps to refine conceptual tenets. In this article we articulate the operational definition and theoretical foundations of the positivity effect and review the empirical evidence based on studies of visual attention, memory, decision-making, and neural activation. We conclude with a discussion of future research directions with emphasis on the conditions where a focus on positive information may benefit and/or impair cognitive performance in older people.

  14. Targeting Mitochondria to Counteract Age-Related Cellular Dysfunction

    Directory of Open Access Journals (Sweden)

    Corina T. Madreiter-Sokolowski

    2018-03-01

    Full Text Available Senescence is related to the loss of cellular homeostasis and functions, which leads to a progressive decline in physiological ability and to aging-associated diseases. Since mitochondria are essential to energy supply, cell differentiation, cell cycle control, intracellular signaling and Ca2+ sequestration, fine-tuning mitochondrial activity appropriately, is a tightrope walk during aging. For instance, the mitochondrial oxidative phosphorylation (OXPHOS ensures a supply of adenosine triphosphate (ATP, but is also the main source of potentially harmful levels of reactive oxygen species (ROS. Moreover, mitochondrial function is strongly linked to mitochondrial Ca2+ homeostasis and mitochondrial shape, which undergo various alterations during aging. Since mitochondria play such a critical role in an organism’s process of aging, they also offer promising targets for manipulation of senescent cellular functions. Accordingly, interventions delaying the onset of age-associated disorders involve the manipulation of mitochondrial function, including caloric restriction (CR or exercise, as well as drugs, such as metformin, aspirin, and polyphenols. In this review, we discuss mitochondria’s role in and impact on cellular aging and their potential to serve as a target for therapeutic interventions against age-related cellular dysfunction.

  15. Cellular models and therapies for age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    David L. Forest

    2015-05-01

    Full Text Available Age-related macular degeneration (AMD is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is caused by the loss of retinal pigmented epithelium (RPE cells and the light-sensitive photoreceptor cells that they support. There is currently no effective treatment for the most common form of this disease (dry AMD. A new approach to treating AMD involves the transplantation of RPE cells derived from either human embryonic or induced pluripotent stem cells. Multiple clinical trials are being initiated using a variety of cell therapies. Although many animal models are available for AMD research, most do not recapitulate all aspects of the disease, hampering progress. However, the use of cultured RPE cells in AMD research is well established and, indeed, some of the more recently described RPE-based models show promise for investigating the molecular mechanisms of AMD and for screening drug candidates. Here, we discuss innovative cell-culture models of AMD and emerging stem-cell-based therapies for the treatment of this vision-robbing disease.

  16. Assessment of Age-Related Changes in Pediatric Gastrointestinal Solubility.

    Science.gov (United States)

    Maharaj, Anil R; Edginton, Andrea N; Fotaki, Nikoletta

    2016-01-01

    Compound solubility serves as a surrogate indicator of oral biopharmaceutical performance. Between infancy and adulthood, marked compositional changes in gastrointestinal (GI) fluids occur. This study serves to assess how developmental changes in GI fluid composition affects compound solubility. Solubility assessments were conducted in vitro using biorelevant media reflective of age-specific pediatric cohorts (i.e., neonates and infants). Previously published adult media (i.e., FaSSGF, FeSSGF, FaSSIF.v2, and FeSSIF.v2) were employed as references for pediatric media development. Investigations assessing age-specific changes in GI fluid parameters (i.e., pepsin, bile acids, pH, osmolality, etc.) were collected from the literature and served to define the composition of neonatal and infant media. Solubility assessments at 37 °C were conducted for seven BCS Class II compounds within the developed pediatric and reference adult media. For six of the seven compounds investigated, solubility fell outside an 80-125% range from adult values in at least one of the developed pediatric media. This result indicates a potential for age-related alterations in oral drug performance, especially for compounds whose absorption is delimited by solubility (i.e., BCS Class II). Developmental changes in GI fluid composition can result in relevant discrepancies in luminal compound solubility between children and adults.

  17. Mechanism of Inflammation in Age-Related Macular Degeneration

    Science.gov (United States)

    Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

    2012-01-01

    Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

  18. Automatic age-related macular degeneration detection and staging

    Science.gov (United States)

    van Grinsven, Mark J. J. P.; Lechanteur, Yara T. E.; van de Ven, Johannes P. H.; van Ginneken, Bram; Theelen, Thomas; Sánchez, Clara I.

    2013-03-01

    Age-related macular degeneration (AMD) is a degenerative disorder of the central part of the retina, which mainly affects older people and leads to permanent loss of vision in advanced stages of the disease. AMD grading of non-advanced AMD patients allows risk assessment for the development of advanced AMD and enables timely treatment of patients, to prevent vision loss. AMD grading is currently performed manually on color fundus images, which is time consuming and expensive. In this paper, we propose a supervised classification method to distinguish patients at high risk to develop advanced AMD from low risk patients and provide an exact AMD stage determination. The method is based on the analysis of the number and size of drusen on color fundus images, as drusen are the early characteristics of AMD. An automatic drusen detection algorithm is used to detect all drusen. A weighted histogram of the detected drusen is constructed to summarize the drusen extension and size and fed into a random forest classifier in order to separate low risk from high risk patients and to allow exact AMD stage determination. Experiments showed that the proposed method achieved similar performance as human observers in distinguishing low risk from high risk AMD patients, obtaining areas under the Receiver Operating Characteristic curve of 0.929 and 0.934. A weighted kappa agreement of 0.641 and 0.622 versus two observers were obtained for AMD stage evaluation. Our method allows for quick and reliable AMD staging at low costs.

  19. The Role of Inflammation in Age-Related Sarcopenia

    Directory of Open Access Journals (Sweden)

    Sebastiaan Dalle

    2017-12-01

    Full Text Available Many physiological changes occur with aging. These changes often, directly or indirectly, result in a deterioration of the quality of life and even in a shortening of life expectancy. Besides increased levels of reactive oxygen species, DNA damage and cell apoptosis, another important factor affecting the aging process involves a systemic chronic low-grade inflammation. This condition has already been shown to be interrelated with several (subclinical conditions, such as insulin resistance, atherosclerosis and Alzheimer's disease. Recent evidence, however, shows that chronic low-grade inflammation also contributes to the loss of muscle mass, strength and functionality, referred to as sarcopenia, as it affects both muscle protein breakdown and synthesis through several signaling pathways. Classic interventions to counteract age-related muscle wasting mainly focus on resistance training and/or protein supplementation to overcome the anabolic inflexibility from which elderly suffer. Although the elderly benefit from these classic interventions, the therapeutic potential of anti-inflammatory strategies is of great interest, as these might add up to/support the anabolic effect of resistance exercise and/or protein supplementation. In this review, the molecular interaction between inflammation, anabolic sensitivity and muscle protein metabolism in sarcopenic elderly will be addressed.

  20. Imaging Polarimetry in Age-Related Macular Degeneration

    Science.gov (United States)

    Miura, Masahiro; Yamanari, Masahiro; Iwasaki, Takuya; Elsner, Ann E.; Makita, Shuichi; Yatagai, Toyohiko; Yasuno, Yoshiaki

    2010-01-01

    PURPOSE To evaluate the birefringence properties of eyes with age-related macular degeneration (AMD). To compare the information from two techniques—scanning laser polarimetry (GDx) and polarization-sensitive spectral-domain optical coherence tomography (OCT)—and investigate how they complement each other. METHODS The authors prospectively examined the eyes of two healthy subjects and 13 patients with exudative AMD. Using scanning laser polarimetry, they computed phase-retardation maps, average reflectance images, and depolarized light images. To obtain polarimetry information with improved axial resolution, they developed a fiber-based, polarization-sensitive, spectral-domain OCT system and measured the phase retardation associated with birefringence in the same eyes. RESULTS Both GDx and polarization-sensitive spectral-domain optical coherence tomography detected abnormal birefringence at the locus of exudative lesions. Polarization-sensitive, spectral-domain OCT showed that in the old lesions with fibrosis, phase-retardation values were significantly larger than in the new lesions (P = 0.020). Increased scattered light and altered polarization scramble were associated with portions of the lesions. CONCLUSIONS GDx and polarization-sensitive spectral-domain OCT are complementary in probing birefringence properties in exudative AMD. Polarimetry findings in exudative AMD emphasized different features and were related to the progression of the disease, potentially providing a noninvasive tool for microstructure in exudative AMD. PMID:18515594

  1. Age related prolactin secretion in men after fentanyl anaesthesia.

    Science.gov (United States)

    Aliberti, Giuseppe; Pulignano, Isabella; Schiappoli, Angelo; Cigognetti, Leonilde; Tritapepe, Luigi; Proietta, Maria

    2002-01-01

    The aim of this study was to investigate the role of age in the hormonal response to opiate anaesthetic fentanyl. In 90 patients undergoing aortocoronary bypass, 59.6 +/- 9.2 years mean age, 35-81 age range, prolactin (PRL), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), luteinizing hormone (LH), human growth hormone (HGH), insulin-like growth factor I (IGF I), glucagon and insulin were measured in venous blood samples drawn from fasting patients immediately before, at 8 h in the morning, and 60 min after the induction of anaesthesia with 30 microg/kg intravenous fentanyl bolus, 30 min after a second 7 microg/kg fentanyl bolus. Results showed a higher 60 min PRL peak in older, >65 years, in respect to younger, 65 and in 51-65-year-olds than in younger patients (for the basal values, respectively, P65 in respect to < or =50 (P<0.02) and to 51-65-year-old patients (P<0.05), with a significant negative correlation with age (r=-0.33; P<0.005). The study shows an age related increase of PRL concentrations after fentanyl administration. It may be due to the reduction of the hypothalamic dopaminergic tone with aging. IGF I levels have been confirmed to be inversely correlated with age.

  2. Die induzierbare antivirale Immunantwort von Drosophila melanogaster

    OpenAIRE

    Kemp, Cordula

    2010-01-01

    In der vorliegenden Arbeit wurde Drosophila melanogaster als Modell ge- nutzt, um die angeborene Immunantwort gegen virale Infektionen zu studie- ren. Wir untersuchten mit Hilfe von genomweiten microarrays das Transkriptom von Fliegen, welche entweder mit dem Drosophila C Virus (DCV), dem Flock- house Virus (FHV) oder dem Sindbis Virus (SINV) infiziert waren. Infektion mit diesen drei positiv orientierten Einzelstrang RNS Viren führte zu einer starken transkriptionellen Antwort, welche deutlic...

  3. Age-Related Changes in CD8 T Cell Homeostasis and Immunity to Infection

    Science.gov (United States)

    Nikolich-Zugich, Janko; Li, Gang; Uhrlaub, Jennifer L.; Renkema, Kristin R.; Smithey, Megan J.

    2012-01-01

    Studies of CD8 T cell responses to vaccination or infection with various pathogens in both animal models and human subjects have revealed a markedly consistent array of age-related defects. In general, recent work shows that aged CD8 T cell responses are decreased in magnitude, and show poor differentiation into effector cells, with a reduced arsenal of effector functions. Here we review potential mechanisms underlying these defects. We specifically address phenotypic and numeric changes to the naïve CD8 T cell precursor pool, the impact of persistent viral infection(s) and inflammation, and contributions of the aging environment in which these cells are activated. PMID:22554418

  4. Flavonoids and oxidative stress in Drosophila melanogaster.

    Science.gov (United States)

    Sotibrán, América Nitxin Castañeda; Ordaz-Téllez, María Guadalupe; Rodríguez-Arnaiz, Rosario

    2011-11-27

    Flavonoids are a family of antioxidants that are widely represented in fruits, vegetables, dry legumes, and chocolate, as well as in popular beverages, such as red wine, coffee, and tea. The flavonoids chlorogenic acid, kaempferol, quercetin and quercetin 3β-d-glycoside were investigated for genotoxicity using the wing somatic mutation and recombination test (SMART). This test makes use of two recessive wing cell markers: multiple wing hairs (mwh) and flare (flr(3)), which are mutations located on the left arm of chromosome 3 of Drosophila melanogaster and are indicative of both mitotic recombination and various types of mutational events. In order to test the antioxidant capacities of the flavonoids, experiments were conducted with various combinations of oxidants and polyphenols. Oxidative stress was induced using hydrogen peroxide, the Fenton reaction and paraquat. Third-instar transheterozygous larvae were chronically treated for all experiments. The data obtained in this study showed that, at the concentrations tested, the flavonoids did not induce somatic mutations or recombination in D. melanogaster with the exception of quercetin, which proved to be genotoxic at only one concentration. The oxidants hydrogen peroxide and the Fenton reaction did not induce mutations in the wing somatic assay of D. melanogaster, while paraquat and combinations of flavonoids produced significant numbers of small single spots. Quercetin 3β-d-glycoside mixed with paraquat was shown to be desmutagenic. Combinations of the oxidants with the other flavonoids did not show any antioxidant activity. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. The influence of Adh function on ethanol preference and tolerance in adult Drosophila melanogaster.

    Science.gov (United States)

    Ogueta, Maite; Cibik, Osman; Eltrop, Rouven; Schneider, Andrea; Scholz, Henrike

    2010-11-01

    Preference determines behavioral choices such as choosing among food sources and mates. One preference-affecting chemical is ethanol, which guides insects to fermenting fruits or leaves. Here, we show that adult Drosophila melanogaster prefer food containing up to 5% ethanol over food without ethanol and avoid food with high levels (23%) of ethanol. Although female and male flies behaved differently at ethanol-containing food sources, there was no sexual dimorphism in the preference for food containing modest ethanol levels. We also investigated whether Drosophila preference, sensitivity and tolerance to ethanol was related to the activity of alcohol dehydrogenase (Adh), the primary ethanol-metabolizing enzyme in D. melanogaster. Impaired Adh function reduced ethanol preference in both D. melanogaster and a related species, D. sechellia. Adh-impaired flies also displayed reduced aversion to high ethanol concentrations, increased sensitivity to the effects of ethanol on postural control, and negative tolerance/sensitization (i.e., a reduction of the increased resistance to ethanol's effects that normally occurs upon repeated exposure). These data strongly indicate a linkage between ethanol-induced behavior and ethanol metabolism in adult fruit flies: Adh deficiency resulted in reduced preference to low ethanol concentrations and reduced aversion to high ones, despite recovery from ethanol being strongly impaired.

  6. Age-related macular degeneration: prevention and treatment. A review

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-07-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA, particularly, docosahexaenoic acid (DHA, are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids. Specific antioxidant food supplement containing ascorbic acid (500 mg, vitamin E (400 IU and beta carotene (15 mg coupled with zinc (80 mg of zinc oxide and copper (2 mg of copper oxide results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It

  7. Age-related macular degeneration: prevention and treatment. A review

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-01-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA, particularly, docosahexaenoic acid (DHA, are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids. Specific antioxidant food supplement containing ascorbic acid (500 mg, vitamin E (400 IU and beta carotene (15 mg coupled with zinc (80 mg of zinc oxide and copper (2 mg of copper oxide results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It

  8. Aflibercept in exudative age related macular degeneration refractory to ranibizumab.

    Science.gov (United States)

    Ruiz Ramos, J; Pascual-Camps, I; Cuéllar-Monreal, M J; Dolz-Marco, R; Fenoll, M A; Font-Noguera, I; Poveda-Andrés, J L; Gallego-Pinazo, R

    2015-12-01

    The aim of this study is to determine the effectiveness, safety and cost of aflibercept in the treatment of wet age-related macular degeneration (ARMD) refractory to ranibizumab. Retrospective observational study was conducted on patients diagnosed with wet ARMD, and previously treated with ranibizumab. Efficacy variables assessed were changes in visual acuity (BCVA) and anatomical improvements in the most affected eye. Factors associated with improvement of BCVA with aflibercept were also studied. Adverse events related to the aflibercept administration were recorded. Cost analysis data were collected from the hospital perspective, and only taking the direct medical costs into account. Cost-effectiveness analysis was calculated using the aflibercept treatment cost, and effectiveness calculated as BCVA gained. A total of 50 eyes corresponding to 46 patients were included. The median follow-up period was 4.6 months (range: 1.0-6.0). Improvement in visual acuity after the first 2 doses and at the end of the follow-up period was observed in 32.0 and 28.0% of treated eyes, respectively. None of the variables studied was associated with an improvement in the BCVA after treatment. No significant differences were found in the average monthly cost between treatments. Aflibercept is shown to be an effective treatment in a significant number of patients resistant to treatment with ranibizumab, presenting a cost similar to that generated during the final stages of treatment with ranibizumab. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  9. DNA damage and repair in age-related macular degeneration

    International Nuclear Information System (INIS)

    Szaflik, Jacek P.; Janik-Papis, Katarzyna; Synowiec, Ewelina; Ksiazek, Dominika; Zaras, Magdalena; Wozniak, Katarzyna; Szaflik, Jerzy; Blasiak, Janusz

    2009-01-01

    Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was grater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.

  10. DNA damage and repair in age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Szaflik, Jacek P. [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Janik-Papis, Katarzyna; Synowiec, Ewelina; Ksiazek, Dominika [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Zaras, Magdalena [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Wozniak, Katarzyna [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Szaflik, Jerzy [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Blasiak, Janusz, E-mail: januszb@biol.uni.lodz.pl [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland)

    2009-10-02

    Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was grater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.

  11. Static and flicker perimetry in age-related macular degeneration.

    Science.gov (United States)

    Luu, Chi D; Dimitrov, Peter N; Wu, Zhichao; Ayton, Lauren N; Makeyeva, Galina; Aung, Khin-Zaw; Varsamidis, Mary; Robman, Luba; Vingrys, Algis J; Guymer, Robyn H

    2013-05-01

    The relationship between clinical severity of age-related macular degeneration (AMD) and macular function has not been well established. In this study, we investigated the correlation between clinical severity and functional deficits as detected by static and flicker perimetry. This cross-sectional study consisted of 279 AMD subjects and 24 control participants. AMD subjects were allocated into 1 of 10 AMD severity groups depending on the status of the designated study eye and the fellow eye, as assessed by color fundus photographs. Visual acuity, and static and flicker perimetry were tested on one eye during the same session. The geometric means, SDs, and percentage of abnormal eyes of static and flicker sensitivity of each AMD severity group were determined and compared. The pattern of change in sensitivity and percentage of abnormal eyes for static perimetry across all AMD severity groups were similar to flicker perimetry. Eyes with drusen > 125 μm (P[static] = 0.018, P[flicker] = 0.024), drusenoid epithelial detachment (P[static and flicker] flicker] flicker sensitivities compared to normal eyes. Static (β-coefficient -1.59, 95% confidence interval [CI] -4.78-1.60) and flicker (β-coefficient -1.29, 95% CI -4.66-2.08) sensitivities declined at a similar rate in eyes that showed clinical signs of progression. Static and flicker perimetry were affected similarly across the spectrum of AMD severity, and methods appeared to be valid techniques for assessing retinal sensitivity in AMD once drusen > 125 μm are present, but before the development of late AMD.

  12. Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy

    Science.gov (United States)

    Ferrer, Isidro; Grinberg, Lea T.; Alafuzoff, Irina; Attems, Johannes; Budka, Herbert; Cairns, Nigel J.; Crary, John F.; Duyckaerts, Charles; Ghetti, Bernardino; Halliday, Glenda M.; Ironside, James W.; Love, Seth; Mackenzie, Ian R.; Munoz, David G.; Murray, Melissa E.; Nelson, Peter T.; Takahashi, Hitoshi; Trojanowski, John Q.; Ansorge, Olaf; Arzberger, Thomas; Baborie, Atik; Beach, Thomas G.; Bieniek, Kevin F.; Bigio, Eileen H.; Bodi, Istvan; Dugger, Brittany N.; Feany, Mel; Gelpi, Ellen; Gentleman, Stephen M.; Giaccone, Giorgio; Hatanpaa, Kimmo J.; Heale, Richard; Hof, Patrick R.; Hofer, Monika; Hortobágyi, Tibor; Jellinger, Kurt; Jicha, Gregory A.; Ince, Paul; Kofler, Julia; Kövari, Enikö; Kril, Jillian J.; Mann, David M.; Matej, Radoslav; McKee, Ann C.; McLean, Catriona; Milenkovic, Ivan; Montine, Thomas J.; Murayama, Shigeo; Lee, Edward B.; Rahimi, Jasmin; Rodriguez, Roberta D.; Rozemüller, Annemieke; Schneider, Julie A.; Schultz, Christian; Seeley, William; Seilhean, Danielle; Smith, Colin; Tagliavini, Fabrizio; Takao, Masaki; Thal, Dietmar Rudolf; Toledo, Jon B.; Tolnay, Markus; Troncoso, Juan C.; Vinters, Harry V.; Weis, Serge; Wharton, Stephen B.; White, Charles L.; Wisniewski, Thomas; Woulfe, John M.; Yamada, Masahito

    2016-01-01

    Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of

  13. Age-related effects in the EEG during propofol anaesthesia.

    Science.gov (United States)

    Schultz, A; Grouven, U; Zander, I; Beger, F A; Siedenberg, M; Schultz, B

    2004-01-01

    Age-related differences in the spectral composition of the EEG in induction and emergence times, and in drug consumption during propofol anaesthesia were investigated. The EEGs of 60 female patients between 22 and 85 years of age were monitored continuously during standardized induction of anaesthesia with 2 mg of propofol kg(-1)60 s(-1). The EEGs were visually assessed in 20-s epochs according to a scale from A (awake) to F (very deep hypnosis). Visual EEG classifications, spectral parameters, and induction times were compared between different age groups. Additionally, data of 546 patients included in a multicentre study with 4630 patients (EEG monitor Narcotrend, MT MonitorTechnik, Bad Bramstedt, Germany) were analyzed with regard to age-dependent changes of propofol consumption using target-controlled infusion (TCI). During induction, patients older than 70 years reached significantly deeper EEG stages than younger patients, needed a longer time to reach the deepest EEG stage, and needed more time until a light EEG stage was regained. In patients aged 70 years and older, the total power, mainly in deep EEG stages, was significantly smaller due to a distinctly smaller absolute power of the delta frequency band. No single spectral parameter was able to reliably distinguish all EEG stages. During the steady state of anaesthesia, older patients needed less propofol for the maintenance of a defined stage of hypnosis than younger patients. Older patients differ from younger ones regarding the hypnotic effect of propofol and the spectral patterns in the EEG. For an efficient automatic assessment of the EEG during anaesthesia a multivariable approach accounting for age-effects is indispensable.

  14. Modelling the genetic risk in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Felix Grassmann

    Full Text Available Late-stage age-related macular degeneration (AMD is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05 than patients aged 75 and above (1.45, 95% CI: 1.36-1.54. Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96 for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population. The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.

  15. Related male Drosophila melanogaster reared together as larvae fight less and sire longer lived daughters

    OpenAIRE

    Carazo, Pau; Perry, Jennifer C; Johnson, Fern; Pizzari, Tommaso; Wigby, Stuart

    2015-01-01

    Competition over access to reproductive opportunities can lead males to harm females. However, recent work has shown that, in Drosophila melanogaster, male competition and male harm of females are both reduced under conditions simulating male-specific population viscosity (i.e., in groups where males are related and reared with each other as larvae). Here, we seek to replicate these findings and investigate whether male population viscosity can have repercussions for the fitness of offspring ...

  16. Effect of gamma irradiation on lifespan and offspring physiology of male drosophila melanogaster

    International Nuclear Information System (INIS)

    Hou Jiangyu; Gu Wei; Jiang Fangping; Han Hetong

    2010-01-01

    This study aimed to investigate the effects of γ-rays irradiation on adult longevity and physiological changes in F 1 generation.Male Drosophila melanogaster at 1 ∼ 2 days old were irradiated by γ-rays with doses of 5, 10, 15 and 30 Gy. In all experimental groups, mean lifespan, maximum lifespan and 90% of lethaldeath irradiated flies were reduced(at P 1 generation of irradiated group, body weight increased, but the capacity of physiological stress declined. (authors)

  17. Dietary Curcumin Ameliorates Aging-Related Cerebrovascular Dysfunction through the AMPK/Uncoupling Protein 2 Pathway

    Directory of Open Access Journals (Sweden)

    Yunfei Pu

    2013-11-01

    Full Text Available Background/Aims: Age-related cerebrovascular dysfunction contributes to stroke, cerebral amyloid angiopathy, cognitive decline and neurodegenerative diseases. One pathogenic mechanism underlying this effect is increased oxidative stress. Up-regulation of mitochondrial uncoupling protein 2 (UCP2 plays a crucial role in regulating reactive oxygen species (ROS production. Dietary patterns are widely recognized as contributors to cardiovascular and cerebrovascular disease. In this study, we tested the hypothesis that dietary curcumin, which has an antioxidant effect, can improve aging-related cerebrovascular dysfunction via UCP2 up-regulation. Methods: The 24-month-old male rodents used in this study, including male Sprague Dawley (SD rats and UCP2 knockout (UCP2-/- and matched wild type mice, were given dietary curcumin (0.2%. The young control rodents were 6-month-old. Rodent cerebral artery vasorelaxation was detected by wire myograph. The AMPK/UCP2 pathway and p-eNOS in cerebrovascular and endothelial cells were observed by immunoblotting. Results: Dietary curcumin administration for one month remarkably restored the impaired cerebrovascular endothelium-dependent vasorelaxation in aging SD rats. In cerebral arteries from aging SD rats and cultured endothelial cells, curcumin promoted eNOS and AMPK phosphorylation, up-regulated UCP2 and reduced ROS production. These effects of curcumin were abolished by either AMPK or UCP2 inhibition. Chronic dietary curcumin significantly reduced ROS production and improved cerebrovascular endothelium-dependent relaxation in aging wild type mice but not in aging UCP2-/- mice. Conclusions: Curcumin improves aging-related cerebrovascular dysfunction via the AMPK/UCP2 pathway.

  18. Nutrition in the age-related disablement process

    NARCIS (Netherlands)

    Inzitari, M.; Doets, E.L.; Bartali, B.; Bari, Di M.; Visser, M.; Volpato, S.; Gambassi, G.; Topinkova, E.; Groot, de C.P.G.M.; Salva, A.

    2011-01-01

    The transition from independence to disability in older adults is characterized by detectable changes in body composition and physical function. Epidemiologic studies have shown that weight loss, reduced caloric intake and the reduced intake of specific nutrients are associated with such changes.

  19. Physiological and psychosocial age-related changes associated with reduced food intake in older persons

    NARCIS (Netherlands)

    de Boer, Antina; Ter Horst, Gert J.; Lorist, Monicque M.

    Dietary intake changes during the course of aging. Normally an increase in food intake is observed around 55 years of age, which is followed by a reduction in food intake in individuals over 65 years of age. This reduction in dietary intake results in lowered levels of body fat and body weight, a

  20. Caring More and Knowing More Reduces Age-Related Differences in Emotion Perception

    Science.gov (United States)

    Stanley, Jennifer Tehan; Isaacowitz, Derek M.

    2015-01-01

    Traditional emotion perception tasks show that older adults are less accurate than young adults at recognizing facial expressions of emotion. Recently, we proposed that socioemotional factors might explain why older adults seem impaired in lab tasks but less so in everyday life (Isaacowitz & Stanley, 2011). Thus, in the present research we empirically tested whether socioemotional factors such as motivation and familiarity can alter this pattern of age effects. In one task, accountability instructions eliminated age differences in the traditional emotion perception task. Using a novel emotion perception paradigm featuring spontaneous dynamic facial expressions of a familiar romantic partner versus a same-age stranger, we found that age differences in emotion perception accuracy were attenuated in the familiar partner condition, relative to the stranger condition. Taken together, the results suggest that both overall accuracy as well as specific patterns of age effects differ appreciably between traditional emotion perception tasks and emotion perception within a socioemotional context. PMID:26030775

  1. Caring more and knowing more reduces age-related differences in emotion perception.

    Science.gov (United States)

    Stanley, Jennifer Tehan; Isaacowitz, Derek M

    2015-06-01

    Traditional emotion perception tasks show that older adults are less accurate than are young adults at recognizing facial expressions of emotion. Recently, we proposed that socioemotional factors might explain why older adults seem impaired in lab tasks but less so in everyday life (Isaacowitz & Stanley, 2011). Thus, in the present research we empirically tested whether socioemotional factors such as motivation and familiarity can alter this pattern of age effects. In 1 task, accountability instructions eliminated age differences in the traditional emotion perception task. Using a novel emotion perception paradigm featuring spontaneous dynamic facial expressions of a familiar romantic partner versus a same-age stranger, we found that age differences in emotion perception accuracy were attenuated in the familiar partner condition, relative to the stranger condition. Taken together, the results suggest that both overall accuracy as well as specific patterns of age effects differ appreciably between traditional emotion perception tasks and emotion perception within a socioemotional context. (c) 2015 APA, all rights reserved.

  2. Oily fish consumption, dietary docosahexaenoic acid and eicosapentaenoic acid intakes, and associations with neovascular age-related macular degeneration

    NARCIS (Netherlands)

    Augood, Cristina; Chakravarthy, Usha; Young, Ian; Vioque, Jesus; de Jong, Paulus T. V. M.; Bentham, Graham; Rahu, Mati; Seland, Johan; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Vingerling, Johannes R.; Fletcher, Astrid E.

    2008-01-01

    Fish intake, the major source of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may reduce the risk of age-related macular degeneration (AMD). We investigated the association of oily fish and dietary DHA and EPA with neovascular AMD (NV-AMD). Participants aged >/=65 y in the

  3. Oxidative stress, innate immunity, and age-related macular degeneration

    Science.gov (United States)

    Shaw, Peter X.; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

    2016-01-01

    Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer’s disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have

  4. Risk factors for endophthalmitis in age-related cataract patients undergoing phacoemulsification

    Directory of Open Access Journals (Sweden)

    Lei Ge

    2018-02-01

    Full Text Available AIM: To explore the risk factors for endophthalmitis in age-related cataract patients undergoing phacoemulsification, in order to provide reasonable intervention countermeasures to reduce the incidence of eddophthalmitis after phacoemulsification, increase the surgery efficacy. METHODS: The 4 500 cases(6 180 eyesof age-related cataract patients with phacoemulsification in our hospital were analyzed, and cases of endopathalmitis needed to have vitreous puncture to collect the sample for analysis, the infectious bacteria, funfal distribution and the operation time, patients age, complications, surgical incision were analyzed for the risk factors of endophthalmitis in senile cataract patients. Data were statistically analyzed by SPSS 18.0.RESULTS: In our study, among the 4500 cases(6180 eyeswith phacoemulsification, the endophthalmitis infection rate was 0.19%(12/6180, the incidence of endophthalmitis was significantly higher in patients with age ≥75 years, with diabetes, hypertension, coronary heart disease history, and the temporal transparent corneal tunnel incision surgery(PPCONCLUSION: For the cataract patients over 75 years old or with diabetes, interventions should be done well before surgery. Surgical incision should be selected in the surgical procedure and avoid complications such as vitreous overflow and posterior capsular rupture in order to reduce the incidence of intraocular infection and improve the postoperative recovery.

  5. Protective effect of myostatin gene deletion on aging-related muscle metabolic decline.

    Science.gov (United States)

    Chabi, B; Pauly, M; Carillon, J; Carnac, G; Favier, F B; Fouret, G; Bonafos, B; Vanterpool, F; Vernus, B; Coudray, C; Feillet-Coudray, C; Bonnieu, A; Lacan, D; Koechlin-Ramonatxo, C

    2016-06-01

    While myostatin gene deletion is a promising therapy to fight muscle loss during aging, this approach induces also skeletal muscle metabolic changes such as mitochondrial deficits, redox alteration and increased fatigability. In the present study, we evaluated the effects of aging on these features in aged wild-type (WT) and mstn knockout (KO) mice. Moreover, to determine whether an enriched-antioxidant diet may be useful to prevent age-related disorders, we orally administered to the two genotypes a melon concentrate rich in superoxide dismutase for 12 weeks. We reported that mitochondrial functional abnormalities persisted (decreased state 3 and 4 of respiration; paged KO mice; however, differences with WT mice were attenuated at old age in line with reduced difference on running endurance between the two genotypes. Interestingly, we showed an increase in glutathione levels, associated with lower lipid peroxidation levels in KO muscle. Enriched antioxidant diet reduced the aging-related negative effects on maximal aerobic velocity and running limit time (p<0.05) in both groups, with systemic adaptations on body weight. The redox status and the hypertrophic phenotype appeared to be beneficial to KO mice, mitigating the effect of aging on the skeletal muscle metabolic remodeling. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Age-related differential item functioning in tests of face and car recognition ability.

    Science.gov (United States)

    Sunday, Mackenzie A; Lee, Woo-Yeol; Gauthier, Isabel

    2018-01-01

    The presence of differential item functioning (DIF) in a test suggests bias that could disadvantage members of a certain group. Previous work with tests of visual learning abilities found significant DIF related to age groups in a car test (Lee, Cho, McGugin, Van Gulick, & Gauthier, 2015), but not in a face test (Cho et al., 2015). The presence of age DIF is a threat to the validity of the test even for studies where aging is not of interest. Here, we assessed whether this pattern of age DIF for cars and not faces would also apply to new tests targeting the same abilities with a new matching task that uses two studied items per trial. We found evidence for DIF in matching tests for faces and for cars, though with encouragingly small effect sizes. Even though the age DIF was small enough at the test level to be acceptable for most uses, we also asked whether the specific format of our matching tasks may induce some age-related DIF regardless of domain. We decomposed the face matching task into its components, and using new data from subjects performing these simpler tasks, found evidence that the age DIF was driven by the similarity of the two faces presented at study on each trial. Overall, our results suggest that using a matching format, especially for cars, reduces age-related DIF, and that a simpler matching task with only one study item per trial could reduce age DIF further.

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

    International Nuclear Information System (INIS)

    Ren, Jian-Ching; Rebrin, Igor; Klichko, Vladimir; Orr, William C.; Sohal, Rajindar S.

    2010-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-10-08

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

  9. Associations between cognitively stimulating leisure activities, cognitive function and age-related cognitive decline.

    Science.gov (United States)

    Ferreira, Nicola; Owen, Adrian; Mohan, Anita; Corbett, Anne; Ballard, Clive

    2015-04-01

    Emerging literature suggests that lifestyle factors may play an important role in reducing age-related cognitive decline. There have, however, been few studies investigating the role of cognitively stimulating leisure activities in maintaining cognitive health. This study sought to identify changes in cognitive performance with age and to investigate associations of cognitive performance with several key cognitively stimulating leisure activities. Over 65,000 participants provided demographic and lifestyle information and completed tests of grammatical reasoning, spatial working memory, verbal working memory and episodic memory. Regression analyses suggested that frequency of engaging in Sudoku or similar puzzles was significantly positively associated with grammatical reasoning, spatial working memory and episodic memory scores. Furthermore, for participants aged under 65 years, frequency of playing non-cognitive training computer games was also positively associated with performance in the same cognitive domains. The results also suggest that grammatical reasoning and episodic memory are particularly vulnerable to age-related decline. Further investigation to determine the potential benefits of participating in Sudoku puzzles and non-cognitive computer games is indicated, particularly as they are associated with grammatical reasoning and episodic memory, cognitive domains found to be strongly associated with age-related cognitive decline. Results of this study have implications for developing improved guidance for the public regarding the potential value of cognitively stimulating leisure activities. The results also suggest that grammatical reasoning and episodic memory should be targeted in developing appropriate outcome measures to assess efficacy of future interventions, and in developing cognitive training programmes to prevent or delay cognitive decline. Copyright © 2014 John Wiley & Sons, Ltd.

  10. Targeting cellular senescence prevents age-related bone loss in mice.

    Science.gov (United States)

    Farr, Joshua N; Xu, Ming; Weivoda, Megan M; Monroe, David G; Fraser, Daniel G; Onken, Jennifer L; Negley, Brittany A; Sfeir, Jad G; Ogrodnik, Mikolaj B; Hachfeld, Christine M; LeBrasseur, Nathan K; Drake, Matthew T; Pignolo, Robert J; Pirtskhalava, Tamar; Tchkonia, Tamara; Oursler, Merry Jo; Kirkland, James L; Khosla, Sundeep

    2017-09-01

    Aging is associated with increased cellular senescence, which is hypothesized to drive the eventual development of multiple comorbidities. Here we investigate a role for senescent cells in age-related bone loss through multiple approaches. In particular, we used either genetic (i.e., the INK-ATTAC 'suicide' transgene encoding an inducible caspase 8 expressed specifically in senescent cells) or pharmacological (i.e., 'senolytic' compounds) means to eliminate senescent cells. We also inhibited the production of the proinflammatory secretome of senescent cells using a JAK inhibitor (JAKi). In aged (20- to 22-month-old) mice with established bone loss, activation of the INK-ATTAC caspase 8 in senescent cells or treatment with senolytics or the JAKi for 2-4 months resulted in higher bone mass and strength and better bone microarchitecture than in vehicle-treated mice. The beneficial effects of targeting senescent cells were due to lower bone resorption with either maintained (trabecular) or higher (cortical) bone formation as compared to vehicle-treated mice. In vitro studies demonstrated that senescent-cell conditioned medium impaired osteoblast mineralization and enhanced osteoclast-progenitor survival, leading to increased osteoclastogenesis. Collectively, these data establish a causal role for senescent cells in bone loss with aging, and demonstrate that targeting these cells has both anti-resorptive and anabolic effects on bone. Given that eliminating senescent cells and/or inhibiting their proinflammatory secretome also improves cardiovascular function, enhances insulin sensitivity, and reduces frailty, targeting this fundamental mechanism to prevent age-related bone loss suggests a novel treatment strategy not only for osteoporosis, but also for multiple age-related comorbidities.

  11. Blueberry-enriched diet ameliorates age-related declines in NMDA receptor-dependent LTP.

    Science.gov (United States)

    Coultrap, Steven J; Bickford, Paula C; Browning, Michael D

    2008-12-01

    NMDA receptor-dependent long-term potentiation (LTP) in the hippocampus is widely accepted as a cellular substrate for memory formation. Age-related declines in the expression of both NMDAR-dependent LTP and NMDAR subunit proteins in the CA1 region of the hippocampus have been well characterized and likely underlie age-related memory impairment. In the current study, we examined NMDAR-dependent LTP in young Fischer 344 rats (4 months old) and aged rats (24 months old) given either a control diet or a diet supplemented with blueberry extract for 6-8 weeks. NMDAR-dependent LTP was evoked by high-frequency stimulation (HFS) in the presence of nifedipine, to eliminate voltage-gated calcium channel LTP. Field excitatory postsynaptic potentials (fEPSPs) were increased by 57% 1 h after HFS in young animals, but this potentiation was reduced to 31% in aged animals. Supplementation of the diet with blueberry extract elevated LTP (63%) in aged animals to levels seen in young. The normalization of LTP may be due to the blueberry diet preventing a decline in synaptic strength, as measured by the slope of the fEPSP for a given fiber potential. The blueberry diet did not prevent age-related declines in NMDAR protein expression. However, phosphorylation of a key tyrosine residue on the NR2B subunit, important for increasing NMDAR function, was enhanced by the diet, suggesting that an increase in NMDAR function might overcome the loss in protein. This report provides evidence that dietary alterations later in life may prevent or postpone the cognitive declines associated with aging.

  12. Age-related reduction of hemispheric lateralisation for spatial attention: An EEG study.

    Science.gov (United States)

    Learmonth, Gemma; Benwell, Christopher S Y; Thut, Gregor; Harvey, Monika

    2017-06-01

    A group-level visuospatial attention bias towards the left side of space (pseudoneglect) is consistently observed in young adults, which is likely to be a consequence of right parieto-occipital dominance for spatial attention. Conversely, healthy older adults demonstrate a rightward shift of this behavioural bias, hinting that an age-related reduction of lateralised neural activity may occur within visuospatial attention networks. We compared young (aged 18-25) and older (aged 60-80) adults on a computerised line bisection (landmark) task whilst recording event-related potentials (ERPs). Full-scalp cluster mass permutation tests identified a larger right parieto-occipital response for long lines compared to short in young adults (confirming Benwell et al., 2014a) which was not present in the older group. To specifically investigate age-related differences in hemispheric lateralisation, cluster mass permutation tests were then performed on a lateralised EEG dataset (RH-LH electrodes). A period of right lateralisation was identified in response to long lines in young adults, which was not present for short lines. No lateralised clusters were present for either long or short lines in older adults. Additionally, a reduced P300 component amplitude was observed for older adults relative to young. We therefore report here, for the first time, an age-related and stimulus-driven reduction of right hemispheric control of spatial attention in older adults. Future studies will need to determine whether this is representative of the normal aging process or an early indicator of neurodegeneration. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Ginkgo biloba extract for age-related macular degeneration.

    Science.gov (United States)

    Evans, Jennifer R

    2013-01-31

    Ginkgo is used in the treatment of peripheral vascular disease and 'cerebral insufficiency'. It is thought to have several potential mechanisms of action including increased blood flow, platelet activating factor antagonism, and prevention of membrane damage caused by free radicals. Vascular factors and oxidative damage are thought to be two potential mechanisms in the pathology of age-related macular degeneration (AMD). The objective of this review was to determine the effect of Ginkgo biloba extract on the progression of AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2012), EMBASE (January 1980 to October 2012), Allied and Complementary Medicine Database (AMED) (January 1985 to October 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 October 2012. We searched the reference lists of identified reports and the Science Citation Index. We also contacted investigators of included studies for additional information. All randomised trials in people with AMD where Ginkgo biloba extract had been compared to control were included. The review author extracted data using a standardised form. The data were verified with the trial investigators. Trial quality was assessed. Two published trials were identified that randomised a total of 119 people. In one study conducted in France, 20 people were randomly allocated to Gingko biloba extract EGb 761 80 mg twice daily or placebo. In

  14. Vision rehabilitation for age-related macular degeneration.

    Science.gov (United States)

    Park, W

    1999-01-01

    Though the numbers of patients with ARMD are high, associated referrals for vision rehabilitation are not. Practitioners need to refer patients with age-related maculopathy when medical and surgical treatment are no longer possible, and patients need to be educated to that fact. The impact of improving activities of daily living may be monumental and benefits society as a whole. People who are visually impaired are often ill-prepared to deal with the substantial adjustment involved, further stressing their entire support system. It may not be safe for visual and systemic reasons for older adults to cook, clean, and maintain their home. Poor vision contributes to the already increased risk of falls and subsequent fractures in these patients. Individuals who may have already been told they can no longer drive now face the possibility of being unable to live in their houses. Their independence may be threatened dramatically and abruptly. All these circumstances contribute to anxiety and depression. Patients with ARMD need to be educated about their disease process (teaching that can never be assumed to have been initiated). They need to be educated that they will not go completely blind and that, with assistance, they can accomplish a great deal. With today's technology, it is not difficult to help visually impaired individuals with ARMD, unless they are not referred or lack motivation. The primary complaint of an individual with ARMD is recognition of central detail. This affects all activities of daily living, and patient performance is subject to the duration and severity of the disease (including the size, density, and location of the central scotoma) and to their understanding of the disease. Rubin and coworkers, found that slow reading performance of patients with a dense central scotoma might reflect inherent limitations of peripheral retina for complex visual tasks. ARMD in most cases lends itself to magnification that enlarges the object beyond the blind spot

  15. Risk factors for age-related maculopathy in a 14-year follow-up study

    DEFF Research Database (Denmark)

    Hesgaard, Helena; Vinding, Troels; la Cour, Morten

    2005-01-01

    To examine the association between potential risk factors and the 14-year incidence of age-related maculopathy (ARM).......To examine the association between potential risk factors and the 14-year incidence of age-related maculopathy (ARM)....

  16. 14-year incidence, progression, and visual morbidity of age-related maculopathy

    DEFF Research Database (Denmark)

    Hesgaard, Helena; Nielsen, Niels V; Vinding, Troels

    2005-01-01

    To describe the 14-year incidence of age-related maculopathy (ARM) lesions and the related visual loss.......To describe the 14-year incidence of age-related maculopathy (ARM) lesions and the related visual loss....

  17. Valeriana officinalis attenuates the rotenone-induced toxicity in Drosophila melanogaster.

    Science.gov (United States)

    Sudati, Jéssie Haigert; Vieira, Francielli Araújo; Pavin, Sandra Sartoretto; Dias, Glaecir Roseni Mundstock; Seeger, Rodrigo Lopes; Golombieski, Ronaldo; Athayde, Margareth Linde; Soares, Félix Antunes; Rocha, João Batista Teixeira; Barbosa, Nilda Vargas

    2013-07-01

    In this study, we investigated the potential protective effects of Valeriana officinalis (V. officinalis) against the toxicity induced by rotenone in Drosophila melanogaster (D. melanogaster). Adult wild-type flies were concomitantly exposed to rotenone (500 μM) and V. officinalis aqueous extract (10mg/mL) in the food during 7 days. Rotenone-fed flies had a worse performance in the negative geotaxis assay (i.e. climbing capability) and open-field test (i.e. mobility time) as well as a higher incidence of mortality when compared to control group. V. officinalis treatment offered protection against these detrimental effects of rotenone. In contrast, the decreased number of crossings observed in the flies exposed to rotenone was not modified by V. officinalis. Rotenone toxicity was also associated with a marked decrease on the total-thiol content in the homogenates and cell viability of flies, which were reduced by V. officinalis treatment. Indeed, rotenone exposure caused a significant increase in the mRNA expression of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and also in the tyrosine hydroxylase (TH) gene. The expression of SOD and CAT mRNAs was normalized by V. officinalis treatment. Our results suggest that V. officinalis extract was effective in reducing the toxicity induced by rotenone in D. melanogaster as well as confirm the utility of this model to investigate potential therapeutic strategies on movement disorders, including Parkinson disease (PD). Copyright © 2013 Elsevier Inc. All rights reserved.

  18. The Association between Plasma 25-Hydroxyvitamin D and Subgroups in Age-Related Macular Degeneration

    DEFF Research Database (Denmark)

    Singh, Amardeep; Falk, Mads Krüger; Subhi, Yousif

    2013-01-01

    To evaluate potential differences in plasma 25-hydroxyvitamin in subtypes of age-related macular degeneration (AMD), and in patients in Clinical Age-Related Maculopathy Staging (CARMS) group 5 with or without subretinal fibrosis.......To evaluate potential differences in plasma 25-hydroxyvitamin in subtypes of age-related macular degeneration (AMD), and in patients in Clinical Age-Related Maculopathy Staging (CARMS) group 5 with or without subretinal fibrosis....

  19. Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

    Energy Technology Data Exchange (ETDEWEB)

    Knecht, Wolfgang [BioCentrum-DTU, Technical University of Denmark, DK-2800 Lyngby (Denmark); Mikkelsen, Nils Egil [Department of Molecular Biology, Swedish University of Agricultural Sciences, Biomedical Centre, SE-751 24 Uppsala (Sweden); Clausen, Anders Ranegaard [Cell and Organism Biology, Lund University, Soelvegatan 35, SE-22362 Lund (Sweden); Willer, Mette [ZGene A/S, Agern Alle 7, DK-2970 Horsholm (Denmark); Eklund, Hans [Department of Molecular Biology, Swedish University of Agricultural Sciences, Biomedical Centre, SE-751 24 Uppsala (Sweden); Gojkovic, Zoran [ZGene A/S, Agern Alle 7, DK-2970 Horsholm (Denmark); Piskur, Jure, E-mail: Jure.Piskur@cob.lu.se [BioCentrum-DTU, Technical University of Denmark, DK-2800 Lyngby (Denmark); Cell and Organism Biology, Lund University, Soelvegatan 35, SE-22362 Lund (Sweden)

    2009-05-01

    Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (Dm-dNK) can additionally sensitize human cancer cell lines towards the anti-cancer drug gemcitabine. We show that this property is based on the Dm-dNK ability to efficiently phosphorylate gemcitabine. The 2.2 A resolution structure of Dm-dNK in complex with gemcitabine shows that the residues Tyr70 and Arg105 play a crucial role in the firm positioning of gemcitabine by extra interactions made by the fluoride atoms. This explains why gemcitabine is a good substrate for Dm-dNK.

  20. Crystal structure of enolase from Drosophila melanogaster.

    Science.gov (United States)

    Sun, Congcong; Xu, Baokui; Liu, Xueyan; Zhang, Zhen; Su, Zhongliang

    2017-04-01

    Enolase is an important enzyme in glycolysis and various biological processes. Its dysfunction is closely associated with diseases. Here, the enolase from Drosophila melanogaster (DmENO) was purified and crystallized. A crystal of DmENO diffracted to 2.0 Å resolution and belonged to space group R32. The structure was solved by molecular replacement. Like most enolases, DmENO forms a homodimer with conserved residues in the dimer interface. DmENO possesses an open conformation in this structure and contains conserved elements for catalytic activity. This work provides a structural basis for further functional and evolutionary studies of enolase.

  1. Age-Related Differences in Quality of Standing Balance Using a Composite Score

    NARCIS (Netherlands)

    Pasma, J.H.; Bijlsma, A.Y.; van der Bij, M.D.W.; Arendzen, J.H.; Meskers, C.G.M.; Maier, A.B.

    2014-01-01

    Background: Age-related differences in standing balance are not detected by testing the ability to maintain balance. Quality of standing balance might be more sensitive to detect age-related differences. Objective: To study age-related differences in quality of standing balance, center of pressure

  2. Neural Alterations in Acquired Age-Related Hearing Loss

    OpenAIRE

    Mudar, Raksha A.; Husain, Fatima T.

    2016-01-01

    Hearing loss is one of the most prevalent chronic health conditions in older adults. Growing evidence suggests that hearing loss is associated with reduced cognitive functioning and incident dementia. In this mini-review, we briefly examine literature on anatomical and functional alterations in the brains of adults with acquired age-associated hearing loss, which may underlie the cognitive consequences observed in this population, focusing on studies that have used structural and functional m...

  3. Age-related changes of MAO-A and -B distribution in human and mouse brain.

    Science.gov (United States)

    Mahy, N; Andrés, N; Andrade, C; Saura, J

    2000-01-01

    Age-related changes of MAO-A and -B were studied in human and BL/C57 mouse brain areas (substantia nigra, putamen and cerebellum). [3H]Ro41-1049 and [3H]lazabemide were used as selective radioligands to image and quantify MAO-A and MAO-B respectively by enzyme autoradiography. MAO-A binding was higher in mouse, whereas MAO-B binding was higher in human. With aging, mouse MAO-A was significantly reduced between 4 and 8 weeks and remained unchanged until 19 months followed by a slight increase between 19 and 25 months. In contrast, no clear variation was observed in humans between the age of 17-93 years. In most of the structures studied a clear age-related increase in MAO-B was observed beginning in mouse brain at 4 weeks, whereas in human tissue this increase started at the age of 50-60 years. These results show marked differences in the levels and variations of mouse and human MAO-A and -B associated with aging and should be taken into account when extrapolating experimental data from mouse to human.

  4. Age-related changes in pharmacodynamics: focus on drugs acting on central nervous and cardiovascular systems.

    Science.gov (United States)

    Trifirò, Gianluca; Spina, Edoardo

    2011-09-01

    Aging is characterized by progressive impairment of functional capacities of all system organs, reduction in homeostatic mechanisms, and altered response to receptor stimulation. These age-related physiologic changes influence both pharmacokinetics and pharmacodynamics of drugs in elderly patients. Pharmacokinetic and pharmacodynamics changes as well as polypharmacy and comorbidities may alter significantly the effect of pharmacological treatment with advancing age. With the same drug concentration at the site of action, significant differences in the response to several drugs have been observed in older patients as compared to younger patients. Elderly patients are particularly suceptibles to the effects of frequently prescribed drugs acting on central nervous system, such as benzodiazepines, antidepressants, antipsychotics and lithium, with high potential for adverse drug reactions. Moreover, in older patients increased sensitivity to warfarin resulting in increased risk of bleeding has been previously documented. On the other hand, reduced effectiveness of conventional doses of cardiovascular drugs, such as diuretics and β-blockers, has been observed. Due to pharmacodynamic changes, therefore, dose adjustment of the above mentioned cardiovascular and psychotropic drugs is recommended in elderly. Clinicians should be aware of the age-related physiologic changes affecting several organ systems and their implications on the effect of drugs that are commonly prescribed to elderly patients.

  5. Nicotinamide phosphoribosyltransferase may be involved in age-related brain diseases.

    Directory of Open Access Journals (Sweden)

    Li-Ying Liu

    Full Text Available Nicotinamide phosphoribosyltransferase (NAMPT is a key enzyme for nicotinamide adenine dinucleotide (NAD biosynthesis, and can be found either intracellularly (iNAMPT or extracellularly (eNAMPT. Studies have shown that both iNAMPT and eNAMPT are implicated in aging and age-related diseases/disorders in the peripheral system. However, their functional roles in aged brain remain to be established. Here we showed that upon aging, NAMPT level increased in serum but decreased in brain, decreased in cortex and hippocampus but remained unchanged in cerebellum and striatum in brain, and increased in microglia but likely decreased in neuron. Accordingly, total NAD (tNAD level significantly decreased in hippocampus, cerebellum and striatum in aged brain. Application of recombinant NAMPT, mimicking the elevated serum NAMPT level, enhanced the susceptibility of cerebral endothelial cells to ischemic injury, while inhibition of iNAMPT by FK866, a specific inhibitor, reduced intracellular NAD level and induced neuronal death. Taken together, we have revealed a region- and cell-specific change of NAMPT level in brain and serum upon aging, deduced its potential consequences, which suggests that NAMPT is a regulatory factor in aging and age-related brain diseases.

  6. Update on Clinical Trials in Dry Age-related Macular Degeneration

    Science.gov (United States)

    Taskintuna, Ibrahim; Elsayed, M. E. A. Abdalla; Schatz, Patrik

    2016-01-01

    This review article summarizes the most recent clinical trials for dry age-related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age-Related Eye Disease Study 2 (AREDS2), implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future. PMID:26957835

  7. Age-related iso-MAC charts for isoflurane, sevoflurane and desflurane in man.

    Science.gov (United States)

    Nickalls, R W D; Mapleson, W W

    2003-08-01

    The motivation for this study was the current difficulty in estimating the total age-related MAC for a patient in a clinical setting. Age-related iso-MAC charts for isoflurane, sevoflurane and desflurane were developed for the clinically useful MAC range (0.6-1.6), age range 5-95 yr, and put in a convenient form for use by practising anaesthetists. The charts are based on Mapleson's meta-analysis (1996) of the available MAC data and can be used to allow for the contribution of nitrous oxide to the total MAC. The charts indicate the influence of age on anaesthetic requirements, showing, for example, that a total MAC of 1.2 using isoflurane and nitrous oxide 67% in oxygen requires an end-expired isoflurane concentration of only 0.25% in a patient of 95 yr vs 1% in a 5-yr-old patient. Colleagues found the charts to be helpful and simple to use clinically. The iso-MAC charts show clearly how patient age can be used to guide the choice of end-expired agent concentration. They also allow a consistent total MAC to be maintained when changing the inspired nitrous oxide concentration, thereby reducing the chance of inadvertent awareness, particularly at the extremes of age.

  8. Age-Related Hearing Loss in Mn-SOD Heterozygous Knockout Mice

    Directory of Open Access Journals (Sweden)

    Makoto Kinoshita

    2013-01-01

    Full Text Available Age-related hearing loss (AHL reduces the quality of life for many elderly individuals. Manganese superoxide dismutase (Mn-SOD, one of the antioxidant enzymes acting within the mitochondria, plays a crucial role in scavenging reactive oxygen species (ROS. To determine whether reduction in Mn-SOD accelerates AHL, we evaluated auditory function in Mn-SOD heterozygous knockout (HET mice and their littermate wild-type (WT C57BL/6 mice by means of auditory brainstem response (ABR. Mean ABR thresholds were significantly increased at 16 months when compared to those at 4 months in both WT and HET mice, but they did not significantly differ between them at either age. The extent of hair cell loss, spiral ganglion cell density, and thickness of the stria vascularis also did not differ between WT and HET mice at either age. At 16 months, immunoreactivity of 8-hydroxydeoxyguanosine was significantly greater in the SGC and SV in HET mice compared to WT mice, but that of 4-hydroxynonenal did not differ between them. These findings suggest that, although decrease of Mn-SOD by half may increase oxidative stress in the cochlea to some extent, it may not be sufficient to accelerate age-related cochlear damage under physiological aging process.

  9. Age-related declines in visuospatial working memory correlate with deficits in explicit motor sequence learning.

    Science.gov (United States)

    Bo, J; Borza, V; Seidler, R D

    2009-11-01

    Numerous studies have shown that older adults exhibit deficits in motor sequence learning, but the mechanisms underlying this effect remain unclear. Our recent work has shown that visuospatial working-memory capacity predicts the rate of motor sequence learning and the length of motor chunks formed during explicit sequence learning in young adults. In the current study, we evaluate whether age-related deficits in working memory explain the reduced rate of motor sequence learning in older adults. We found that older adults exhibited a correlation between visuospatial working-memory capacity and motor sequence chunk length, as we observed previously in young adults. In addition, older adults exhibited an overall reduction in both working-memory capacity and motor chunk length compared with that of young adults. However, individual variations in visuospatial working-memory capacity did not correlate with the rate of learning in older adults. These results indicate that working memory declines with age at least partially explain age-related differences in explicit motor sequence learning.

  10. Age-related effect of cell death on fiber morphology and number in tongue muscle.

    Science.gov (United States)

    Kletzien, Heidi; Hare, Allison J; Leverson, Glen; Connor, Nadine P

    2018-01-01

    Multiple pathways may exist for age-related tongue muscle degeneration. Cell death is one mechanism contributing to muscle atrophy and decreased function. We hypothesized with aging, apoptosis, and apoptotic regulators would be increased, and muscle fiber size and number would be reduced in extrinsic tongue muscles. Cell death indices, expression of caspase-3 and Bcl-2, and measures of muscle morphology and number were determined in extrinsic tongue muscles of young and old rats. Significant increases in cell death, caspase-3, and Bcl-2 were observed in all extrinsic tongue muscles along with reductions in muscle fiber number in old rats. We demonstrated that apoptosis indices increase with age in lingual muscles and that alterations in apoptotic regulators may be associated with age-related degeneration in muscle fiber size and number. These observed apoptotic processes may be detrimental to muscle function, and may contribute to degradation of cranial functions with age. Muscle Nerve 57: E29-E37, 2018. © 2017 Wiley Periodicals, Inc.

  11. Dietary consumption of monosodium L-glutamate induces adaptive response and reduction in the life span of Drosophila melanogaster.

    Science.gov (United States)

    Abolaji, Amos O; Olaiya, Charles O; Oluwadahunsi, Oluwagbenga J; Farombi, Ebenezer O

    2017-04-01

    Adaptive response is the ability of an organism to better counterattack stress-induced damage in response to a number of different cytotoxic agents. Monosodium L-glutamate (MSG), the sodium salt of amino acid glutamate, is commonly used as a food additive. We investigated the effects of MSG on the life span and antioxidant response in Drosophila melanogaster (D. melanogaster). Both genders (1 to 3 days old) of flies were fed with diet containing MSG (0.1, 0.5, and 2.5-g/kg diet) for 5 days to assess selected antioxidant and oxidative stress markers, while flies for longevity were fed for lifetime. Thereafter, the longevity assay, hydrogen peroxide (H 2 O 2 ), and reactive oxygen and nitrogen species levels were determined. Also, catalase, glutathione S-transferase and acetylcholinesterase activities, and total thiol content were evaluated in the flies. We found that MSG reduced the life span of the flies by up to 23% after continuous exposure. Also, MSG increased reactive oxygen and nitrogen species and H 2 O 2 generations and total thiol content as well as the activities of catalase and glutathione S-transferase in D. melanogaster (P melanogaster induced adaptive response, but long-term exposure reduced life span of flies. This study may therefore have public health significance in humans, and thus, moderate consumption of MSG is advocated by the authors. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Recent developments in the management of dry age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Buschini E

    2015-04-01

    Full Text Available Elisa Buschini, Antonio M Fea, Carlo A Lavia, Marco Nassisi, Giulia Pignata, Marta Zola, Federico M Grignolo Ospedale Oftalmico, Ophthalmic Section, Department of Clinical Pathophysiology, University of Turin, Turin, Italy Abstract: Dry age-related macular degeneration (AMD, also called geographic atrophy, is characterized by the atrophy of outer retinal layers and retinal pigment epithelium (RPE cells. Dry AMD accounts for 80% of all intermediate and advanced forms of the disease. Although vision loss is mainly due to the neovascular form (75%, dry AMD remains a challenge for ophthalmologists because of the lack of effective therapies. Actual management consists of lifestyle modification, vitamin supplements, and supportive measures in the advanced stages. The Age-Related Eye Disease Study demonstrated a statistically significant protective effect of dietary supplementation of antioxidants (vitamin C, vitamin E, beta-carotene, zinc, and copper on dry AMD progression rate. It was also stated that the consumption of omega-3 polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid, has protective effects. Other antioxidants, vitamins, and minerals (such as crocetin, curcumin, and vitamins B9, B12, and B6 are under evaluation, but the results are still uncertain. New strategies aim to 1 reduce or block drusen formation, 2 reduce or eliminate inflammation, 3 lower the accumulation of toxic by-products from the visual cycle, 4 reduce or eliminate retinal oxidative stress, 5 improve choroidal perfusion, 6 replace/repair or regenerate lost RPE cells and photoreceptors with stem cell therapy, and 7 develop a target gene therapy. Keywords: dry AMD, geographic atrophy, new AMD therapy

  13. Structure of PCNA from Drosophila melanogaster

    International Nuclear Information System (INIS)

    Wang, Ke; Shi, Zhubing; Zhang, Min; Cheng, Dianlin

    2013-01-01

    Proliferating cell nuclear antigen (PCNA) plays essential roles in DNA replication, DNA repair, cell-cycle regulation and chromatin metabolism. The PCNA from Drosophila melanogaster (DmPCNA) has been purified and crystallized. Proliferating cell nuclear antigen (PCNA) plays essential roles in DNA replication, DNA repair, cell-cycle regulation and chromatin metabolism. The PCNA from Drosophila melanogaster (DmPCNA) was purified and crystallized. The crystal of DmPCNA diffracted to 2.0 Å resolution and belonged to space group H3, with unit-cell parameters a = b = 151.16, c = 38.28 Å. The structure of DmPCNA was determined by molecular replacement. DmPCNA forms a symmetric homotrimer in a head-to-tail manner. An interdomain connector loop (IDCL) links the N- and C-terminal domains. Additionally, the N-terminal and C-terminal domains contact each other through hydrophobic associations. Compared with human PCNA, the IDCL of DmPCNA has conformational changes, which may explain their difference in function. This work provides a structural basis for further functional and evolutionary studies of PCNA

  14. A sensory origin for color-word stroop effects in aging: simulating age-related changes in color-vision mimics age-related changes in Stroop.

    Science.gov (United States)

    Ben-David, Boaz M; Schneider, Bruce A

    2010-11-01

    An increase in Stroop effects with age can be interpreted as reflecting age-related reductions in selective attention, cognitive slowing, or color-vision. In the present study, 88 younger adults performed a Stroop test with two color-sets, saturated and desaturated, to simulate an age-related decrease in color perception. This color manipulation with younger adults was sufficient to lead to an increase in Stroop effects that mimics age-effects. We conclude that age-related changes in color perception can contribute to the differences in Stroop effects observed in aging. Finally, we suggest that the clinical applications of Stroop take this factor into account.

  15. Age-Related Psychophysical Changes and Low Vision

    Science.gov (United States)

    Dagnelie, Gislin

    2013-01-01

    When considering the burden of visual impairment on aging individuals and society at large, it is important to bear in mind that vision changes are a natural aspect of aging. In this article, we consider vision changes that are part of normal aging, the prevalence of abnormal vision changes caused by disorders of the visual system, and the anticipated incidence and impact of visual impairment as the US population ages. We then discuss the services available to reduce the impact of vision loss, and the extent to which those services can and should be improved, not only to be better prepared for the anticipated increase in low vision over the coming decades, but also to increase the awareness of interactions between visual impairment and comorbidities that are common among the elderly. Finally, we consider how to promote improved quality, availability, and acceptance of low vision care to lessen the impact of visual impairment on individuals, and its burden on society. PMID:24335074

  16. Impact of the resident microbiota on the nutritional phenotype of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Emma V Ridley

    Full Text Available Animals are chronically infected by benign and beneficial microorganisms that generally promote animal health through their effects on the nutrition, immune function and other physiological systems of the host. Insight into the host-microbial interactions can be obtained by comparing the traits of animals experimentally deprived of their microbiota and untreated animals. Drosophila melanogaster is an experimentally tractable system to study host-microbial interactions.The nutritional significance of the microbiota was investigated in D. melanogaster bearing unmanipulated microbiota, demonstrated by 454 sequencing of 16S rRNA amplicons to be dominated by the α-proteobacterium Acetobacter, and experimentally deprived of the microbiota by egg dechorionation (conventional and axenic flies, respectively. In axenic flies, larval development rate was depressed with no effect on adult size relative to conventional flies, indicating that the microbiota promotes larval growth rates. Female fecundity did not differ significantly between conventional and axenic flies, but axenic flies had significantly reduced metabolic rate and altered carbohydrate allocation, including elevated glucose levels.We have shown that elimination of the resident microbiota extends larval development and perturbs energy homeostasis and carbohydrate allocation patterns of of D. melanogaster. Our results indicate that the resident microbiota promotes host nutrition and interacts with the regulation of host metabolism.

  17. Wolbachia influences the maternal transmission of the gypsy endogenous retrovirus in Drosophila melanogaster.

    Science.gov (United States)

    Touret, Franck; Guiguen, François; Terzian, Christophe

    2014-09-02

    The endosymbiotic bacteria of the genus Wolbachia are present in most insects and are maternally transmitted through the germline. Moreover, these intracellular bacteria exert antiviral activity against insect RNA viruses, as in Drosophila melanogaster, which could explain the prevalence of Wolbachia bacteria in natural populations. Wolbachia is maternally transmitted in D. melanogaster through a mechanism that involves distribution at the posterior pole of mature oocytes and then incorporation into the pole cells of the embryos. In parallel, maternal transmission of several endogenous retroviruses is well documented in D. melanogaster. Notably, gypsy retrovirus is expressed in permissive follicle cells and transferred to the oocyte and then to the offspring by integrating into their genomes. Here, we show that the presence of Wolbachia wMel reduces the rate of gypsy insertion into the ovo gene. However, the presence of Wolbachia does not modify the expression levels of gypsy RNA and envelope glycoprotein from either permissive or restrictive ovaries. Moreover, Wolbachia affects the pattern of distribution of the retroviral particles and the gypsy envelope protein in permissive follicle cells. Altogether, our results enlarge the knowledge of the antiviral activity of Wolbachia to include reducing the maternal transmission of endogenous retroviruses in D. melanogaster. Animals have established complex relationships with bacteria and viruses that spread horizontally among individuals or are vertically transmitted, i.e., from parents to offspring. It is well established that members of the genus Wolbachia, maternally inherited symbiotic bacteria present mainly in arthropods, reduce the replication of several RNA viruses transmitted horizontally. Here, we demonstrate for the first time that Wolbachia diminishes the maternal transmission of gypsy, an endogenous retrovirus in Drosophila melanogaster. We hypothesize that gypsy cannot efficiently integrate into the germ

  18. Age-related changes in CD8 T cell homeostasis and immunity to infection.

    Science.gov (United States)

    Nikolich-Žugich, Janko; Li, Gang; Uhrlaub, Jennifer L; Renkema, Kristin R; Smithey, Megan J

    2012-10-01

    Studies of CD8 T cell responses to vaccination or infection with various pathogens in both animal models and human subjects have revealed a markedly consistent array of age-related defects. In general, recent work shows that aged CD8 T cell responses are decreased in magnitude, and show poor differentiation into effector cells, with a reduced arsenal of effector functions. Here we review potential mechanisms underlying these defects. We specifically address phenotypic and numeric changes to the naïve CD8 T cell precursor pool, the impact of persistent viral infection(s) and inflammation, and contributions of the aging environment in which these cells are activated. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Vagal Recovery From Cognitive Challenge Moderates Age-Related Deficits in Executive Functioning

    Science.gov (United States)

    Crowley, Olga V.; Kimhy, David; McKinley, Paula S.; Burg, Matthew M.; Schwartz, Joseph E.; Lachman, Margie E.; Tun, Patricia A.; Ryff, Carol D.; Seeman, Teresa E.; Sloan, Richard P.

    2015-01-01

    Decline in executive functioning (EF) is a hallmark of cognitive aging. We have previously reported that faster vagal recovery from cognitive challenge is associated with better EF. This study examined the association between vagal recovery from cognitive challenge and age-related differences in EF among 817 participants in the Midlife in the U.S. study (aged 35–86). Cardiac vagal control was measured as high-frequency heart rate variability. Vagal recovery moderated the association between age and EF (β = .811, p = .004). Secondary analyses revealed that older participants (aged 65–86) with faster vagal recovery had superior EF compared to their peers who had slower vagal recovery. In contrast, among younger (aged 35–54) and middle-aged (aged 55–64) participants, vagal recovery was not associated with EF. We conclude that faster vagal recovery from cognitive challenge is associated with reduced deficits in EF among older, but not younger individuals. PMID:26303063

  20. Bevacizumab (Avastin) conjugated microbubbles for anti-VEGF treatment of neovascular age-related macular degeneration

    Science.gov (United States)

    Zhang, Leilei; Xu, Jeff; Huang, Jiwei; Roberts, Cynthia; Xu, Ronald

    2010-02-01

    Bevacizumab (Avastin) has been used as one of the anti-VEGF therapies to manage neovascular age-related macular degeneration (AMD). The drug delivery system for bevacizumab needs to be improved in order to decrease the frequency of injection and reduce the adverse effects. In our study, bevacizumab was conjugated with poly (lactic-co-glycolic acid) (PLGA) microbubbles by activating carboxyl functional groups. The averaged size of microbubbles was estimated 1.055+/-0.258μm, allowing for ultrasound guided drug delivery. The binding efficiency between bevacizumab and microbubbles was evaluated in an enzyme-linked immunosorbent assay plate. The test results demonstrated the potential of using PLGA microbubbles to deliver bevacizumab with imaging guidance.

  1. Age-related binding deficits and the content of false memories.

    Science.gov (United States)

    Lyle, Keith B; Bloise, Suzanne M; Johnson, Marcia K

    2006-03-01

    The authors examined effects of age-related binding deficits on feature information in false memories for imagined objects (e.g., lollipop) that were similar in shape to seen objects (e.g., magnifying glass). In Experiment 1, location memory for seen objects was lower in older than younger adults and lower still in old-old than young-old adults. Imagined objects, when falsely called seen, were less likely to be attributed to the location of similar seen objects (i.e., congruent attributions) by old-old than young-old adults. In Experiment 2, for younger adults, displaying seen objects for less time (1 s vs. 4 s) reduced both location memory for seen objects and congruent attributions for false memories. Thus, binding deficits may influence the specific content of false memories. ((c) 2006 APA, all rights reserved).

  2. Neural correlates of age-related decline and compensation in visual attention capacity

    DEFF Research Database (Denmark)

    Wiegand, Iris; Töllner, Thomas; Dyrholm, Mads

    2014-01-01

    participants. In both age groups, the same distinct components indexed performance levels of TVA parameters visual processing speed C and visual short-term memory (vSTM) storage capacity K: The posterior N1 marked interindividual differences in C and the contralateral delay activity (CDA) marked inter......We identified neural correlates of declined and preserved basic visual attention functions in aging individuals based on Bundesen’s ‘Theory of Visual Attention’ (TVA). In an inter-individual difference approach, we contrasted electrophysiology of higher- and lower-performing younger and older......-individual differences in K. Moreover, both parameters were selectively related to two further ERP waves in older age: The anterior N1 was reduced for older participants with lower processing speed, indicating that age-related loss of attentional resources slows encoding. An enhanced right-central positivity (RCP...

  3. Association of gait and balance disorders with age-related white matter changes: the LADIS study

    DEFF Research Database (Denmark)

    Baezner, H.; Blahak, C.; Poggesi, A.

    2008-01-01

    . Quantitative tests of gait and balance include the Short Physical Performance Battery (SPPB; range: 0 [poor] to 12 [normal]), a timed 8-m walk, and a timed single leg stance test. RESULTS: In cross-sectional analysis, deficiencies in gait and balance performance were correlated with the severity of ARWMC (SPPB...... on different objective measures of gait and balance. METHODS: Six hundred thirty-nine nondisabled individuals were prospectively enrolled and are being followed-up for 3 years. Subjects are graded in three standardized categories of ARWMC (mild, moderate, and severe) according to central MRI reading......% CI 1.02 to 2.52; severe vs mild ARWMC: odds ratio 1.75, 95% CI 1.09 to 2.80). CONCLUSIONS: Our findings support a strong association between the severity of age-related white matter changes and the severity of gait and motor compromise. Physical activity might have the potential to reduce the risk...

  4. Age-related changes in skeletal muscle mitochondria: the role of exercise

    Directory of Open Access Journals (Sweden)

    Dae Yun Seo

    2016-09-01

    Full Text Available Aging is associated with mitochondrial dysfunction, which leads to a decline in cellular function and the development of age-related diseases. Reduced skeletal muscle mass with aging appears to promote a decrease in mitochondrial quality and quantity. Moreover, mitochondrial dysfunction adversely affects the quality and quantity of skeletal muscle. During aging, physical exercise can cause beneficial adaptations to cellular energy metabolism in skeletal muscle, including alterations to mitochondrial content, protein, and biogenesis. Here, we briefly summarize current findings on the association between the aging process and impairment of mitochondrial function, including mitochondrial biogenesis and reactive oxygen species in skeletal muscle. We also discuss the potential role of exercise in the improvement of aging-driven mitochondrial dysfunctions.

  5. Mediterranean Diet Score and Its Association with Age-Related Macular Degeneration: The European Eye Study.

    Science.gov (United States)

    Hogg, Ruth E; Woodside, Jayne V; McGrath, Alanna; Young, Ian S; Vioque, Jesus L; Chakravarthy, Usha; de Jong, Paulus T; Rahu, Mati; Seland, Johan; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Fletcher, Astrid E

    2017-01-01

    To examine associations between adherence to a Mediterranean diet and prevalence of age-related macular degeneration (AMD) in countries ranging from Southern to Northern Europe. Cross-sectional, population-based epidemiologic study. Of 5060 randomly sampled people aged 65 years or older from 7 study centers across Europe (Norway, Estonia, United Kingdom, France, Italy, Greece, and Spain), full dietary data were available in 4753. The mean age of participants was 73.2 years (standard deviation, 5.6), and 55% were women. Participants underwent an eye examination and digital retinal color photography. The images were graded at a single center. Dietary intake during the previous 12 months was assessed by using a semiquantitative food-frequency questionnaire (FFQ). A previously published Mediterranean Diet Score (MDS) was used to classify participants according to their responses on the FFQ. Multivariable logistic regression was used to investigate the association of the MDS score and AMD, taking account of potential confounders and the multicenter study design. Images were graded according to the International Classification System for age-related maculopathy and stratified using the Rotterdam staging system into 5 exclusive stages (AMD 0-4) and a separate category of large drusen (≥125 μm). Age-related macular degeneration 4 included neovascular AMD (nvAMD) and geographic atrophy (GA). Increasing MDS was associated with reduced odds of nvAMD in unadjusted and confounder-adjusted analysis. Compared with the lowest MDS adherence (≤4 score), those in the highest category MDS adherence (>6 score) showed lower odds of nvAMD (odds ratio, 0.53; 0.27-1.04; P trend = 0.01). The association with MDS did not differ by Y204H risk allele (P = 0.89). For all early AMD (grade 1-3), there was no relationship with MDS (P trend = 0.9). There was a weak trend (P = 0.1) between MDS and large drusen; those in the highest category of MDS had 20% reduced odds compared with those in

  6. Neural Alterations in Acquired Age-Related Hearing Loss

    Science.gov (United States)

    Mudar, Raksha A.; Husain, Fatima T.

    2016-01-01

    Hearing loss is one of the most prevalent chronic health conditions in older adults. Growing evidence suggests that hearing loss is associated with reduced cognitive functioning and incident dementia. In this mini-review, we briefly examine literature on anatomical and functional alterations in the brains of adults with acquired age-associated hearing loss, which may underlie the cognitive consequences observed in this population, focusing on studies that have used structural and functional magnetic resonance imaging, diffusion tensor imaging, and event-related electroencephalography. We discuss structural and functional alterations observed in the temporal and frontal cortices and the limbic system. These neural alterations are discussed in the context of common cause, information-degradation, and sensory-deprivation hypotheses, and we suggest possible rehabilitation strategies. Although, we are beginning to learn more about changes in neural architecture and functionality related to age-associated hearing loss, much work remains to be done. Understanding the neural alterations will provide objective markers for early identification of neural consequences of age-associated hearing loss and for evaluating benefits of intervention approaches. PMID:27313556

  7. Neural Alterations in Acquired Age-Related Hearing Loss

    Directory of Open Access Journals (Sweden)

    Raksha Anand Mudar

    2016-06-01

    Full Text Available Hearing loss is one of the most prevalent chronic health conditions in older adults. Growing evidence suggests that hearing loss is associated with reduced cognitive functioning and incident dementia. In this mini-review, we briefly examine literature on anatomical and functional alterations in the brains of adults with acquired age-associated hearing loss, which may underlie the cognitive consequences observed in this population, focusing on studies that have used structural and functional magnetic resonance imaging, diffusion tensor imaging, and event-related electroencephalography. We discuss structural and functional alterations observed in the temporal and frontal cortices and the limbic system. These neural alterations are discussed in the context of common cause, information-degradation, and sensory-deprivation hypotheses, and we suggest possible rehabilitation strategies. Although we are beginning to learn more about changes in neural architecture and functionality related to age-associated hearing loss, much work remains to be done. Understanding the neural alterations will provide objective markers for early identification of neural consequences of age-associated hearing loss and for evaluating benefits of intervention approaches.

  8. Dosimetric implications of age related glandular changes in screening mammography

    International Nuclear Information System (INIS)

    Beckett, J.R.; Kotre, C.J.

    2000-01-01

    The UK National Health Service Breast Screening Programme is currently organized to routinely screen women between the ages of 50 and 64, with screening for older women available on request. The lower end of this age range closely matches the median age for the menopause (51 years), during which significant changes in the composition of the breast are known to occur. In order to quantify the dosimetric effect of these changes, radiographic factors and compressed breast thickness data for a cohort of 1258 women aged between 35 and 79 undergoing breast screening mammography have been used to derive estimates of breast glandularity and mean glandular dose (MGD), and examine their variation with age. The variation of mean radiographic exposure factors with age is also investigated. The presence of a significant number of age trial women within the cohort allowed an extended age range to be studied. Estimates of MGD including corrections for breast glandularity based on compressed breast thickness only, compressed breast thickness and age and for each individual woman are compared with the MGD based on the conventional assumption of a 50:50 adipose/glandular composition. It has been found that the use of the conventional 50:50 assumption leads to overestimates of MGD of up to 13% over the age range considered. By using compressed breast thickness to estimate breast glandularity, this error range can be reduced to 8%, whilst age and compressed breast thickness based glandularity estimates result in an error range of 1%. (author)

  9. Hormetic efficacy of rutin to promote longevity in Drosophila melanogaster.

    Science.gov (United States)

    Chattopadhyay, Debarati; Chitnis, Atith; Talekar, Aishwarya; Mulay, Prajakta; Makkar, Manyata; James, Joel; Thirumurugan, Kavitha

    2017-06-01

    Hormetins are compounds that mediate hormesis by being beneficial at low doses but detrimental at high doses. Recent studies have highlighted that many compounds that extended lifespan in model organisms did so by mediating hormesis. Rutin is a glycosylate conjugate of quercetin and rutinose and is abundant in citrus fruits and buckwheat seeds. Rutin possess ROS scavenging, anti-cancer, cardio-protective, skin-regenerative and neuro-protective properties. Drosophila melanogaster is an attractive model organism for longevity studies owing to its homology of organ and cellular-pathways with mammals. In this study, we aimed to understand the effect of rutin on extending longevity in Drosophila melanogaster. Male and female flies were administered with a range of rutin doses (100-800 µM) to analyse whether rutin mediated lifespan-extension by hormesis. Effect of rutin on physiological parameters like food intake, fecundity, climbing activity, development and resistance to various stresses was also studied. Lifespan assays showed that rutin at 200 and 400 µM significantly extended median lifespan in both male and female flies beyond which flies exhibited drastically reduced longevity. Increase in survival at 400 µM was associated with reduced food intake and fecundity. Flies exhibited improved climbing capability with both 200 and 400 µM rutin. Flies fed with 100 and 200 µM rutin exhibited enhanced survival upon exposure to oxidative stress with 400 µM rutin exhibiting no improvement in median lifespan following oxidative stress. Analysis of endogenous peroxide upon treatment with rutin (100-400 µM) with or without 5% H 2 O 2 showed elevated levels of endogenous peroxide with 400 µM rutin whereas no increase in hydrogen peroxide level was observed with rutin at 100 and 200 µM. Finally, gene expression studies in male flies revealed that rutin treatment at 200 and/or 400 µM elevated transcript levels of dFoxO, MnSod, Cat, dTsc1, dTsc2, Thor, dAtg1, d

  10. The Combined Effect of Methyl- and Ethyl-Paraben on Lifespan and Preadult Development Period of Drosophila melanogaster (Diptera: Drosophilidae).

    Science.gov (United States)

    Chen, Qi; Pan, Chenguang; Li, Yajuan; Zhang, Min; Gu, Wei

    2016-01-01

    Parabens are widely used as preservative substances in foods, pharmaceuticals, industrial products, and cosmetics. But several studies have cautioned that parabens have estrogenic or endocrine-disrupting properties. Drosophila melanogaster is an ideal model in vivo to detect the toxic effects of chemistry. The study was designed to assess the potential additive toxic effects of methylparaben (MP) and ethylparaben (EP) mixture (MP + EP) on lifespan and preadult development period in D. melanogaster The data revealed that the MP + EP can reduce the longevity of flies compared with the control group, consistent with a significant reduction in malondialdehyde levels and an increase in superoxide dismutase activities. Furthermore, MP + EP may have a greater toxic effect on longevity of flies than separate using with the same concentration. Additionally, parabens had a nonmonotonic dose-response effect on D. melanogaster preadult development period, showing that MP + EP delayed preadult development period compared with control group while individual MP or EP significantly shortened (P melanogaster. © The Author 2016. Published by Oxford University Press on behalf of the Entomological Society of America.

  11. The Combined Effect of Methyl- and Ethyl-Paraben on Lifespan and Preadult Development Period of Drosophila melanogaster (Diptera: Drosophilidae)

    Science.gov (United States)

    Chen, Qi; Pan, Chenguang; Li, Yajuan; Zhang, Min; Gu, Wei

    2016-01-01

    Parabens are widely used as preservative substances in foods, pharmaceuticals, industrial products, and cosmetics. But several studies have cautioned that parabens have estrogenic or endocrine-disrupting properties. Drosophila melanogaster is an ideal model in vivo to detect the toxic effects of chemistry. The study was designed to assess the potential additive toxic effects of methylparaben (MP) and ethylparaben (EP) mixture (MP + EP) on lifespan and preadult development period in D. melanogaster. The data revealed that the MP + EP can reduce the longevity of flies compared with the control group, consistent with a significant reduction in malondialdehyde levels and an increase in superoxide dismutase activities. Furthermore, MP + EP may have a greater toxic effect on longevity of flies than separate using with the same concentration. Additionally, parabens had a nonmonotonic dose–response effect on D. melanogaster preadult development period, showing that MP + EP delayed preadult development period compared with control group while individual MP or EP significantly shortened (P < 0.01) at low concentration (300 mg/l). In conclusion, MP + EP had the potential additive toxicity on lifespan and preadult development period for D. melanogaster. PMID:28076277

  12. Electrical stimulation attenuates denervation and age-related atrophy in extensor digitorum longus muscles of old rats.

    Science.gov (United States)

    Dow, Douglas E; Dennis, Robert G; Faulkner, John A

    2005-04-01

    Skeletal muscles of old rats and elderly humans lose muscle mass and maximum force. Denervation is a major cause of age-related muscle atrophy and weakness, because denervated fibers do not contract, and undergo atrophy. At any age, surgical denervation causes even more dramatic muscle atrophy and loss in force than aging does. Electrical stimulation that generates tetanic contractions of denervated muscles reduces the denervation-induced declines. We investigated whether a stimulation protocol that maintains mass and force of denervated extensor digitorum longus muscles of adult rats would also maintain these properties in denervated muscles of old rats during a 2-month period of age-induced declines in these properties. Contractile activity generated by the electrical stimulation eliminated age-related losses in muscle mass and reduced the deficit in force by 50%. These data provide support for the hypothesis that during aging, lack of contractile activity in fibers contributes to muscle atrophy and weakness.

  13. Neurogenetics of female reproductive behaviors in Drosophila melanogaster

    NARCIS (Netherlands)

    Laturney, Meghan; Billeter, Jean-Christophe; Friedmann, T; Dunlap, JC; Goodwin, SF

    2014-01-01

    We follow an adult Drosophila melanogaster female through the major reproductive decisions she makes during her lifetime, including habitat selection, precopulatory mate choice, postcopulatory physiological changes, polyandry, and egg-laying site selection. In the process, we review the molecular

  14. Induction of morphological aberrations by enzyme inhibition in Drosophila melanogaster

    NARCIS (Netherlands)

    Bos, M.; Scharloo, W.; Bijlsma, R.; de Boer, I.M.; den Hollander, J.

    1969-01-01

    Zusatz zum Futter vonDrosophila melanogaster von 5-Fluoro-2-deoxyuridin oder Aminopterin induziert überzählige Skutellar- und Dorsozentralborsten sowie gekerbte Flügel. Diese Modifikationen wurden als Konsequenz von Enzymhemmung interpretiert.

  15. A high-quality catalog of the Drosophila melanogaster proteome

    DEFF Research Database (Denmark)

    Brunner, Erich; Ahrens, Christian H.; Mohanty, Sonaly

    2007-01-01

    % of the predicted Drosophila melanogaster proteome by detecting 9,124 proteins from 498,000 redundant and 72,281 distinct peptide identifications. This unprecedented high proteome coverage for a complex eukaryote was achieved by combining sample diversity, multidimensional biochemical fractionation and analysis...... matching approximately 50% of D. melanogaster gene models. This library of proteotypic peptides should enable fast, targeted and quantitative proteomic studies to elucidate the systems biology of this model organism....

  16. Maintenance of a Drosophila melanogaster Population Cage.

    Science.gov (United States)

    Caravaca, Juan Manuel; Lei, Elissa P

    2016-03-15

    Large quantities of DNA, RNA, proteins and other cellular components are often required for biochemistry and molecular biology experiments. The short life cycle of Drosophila enables collection of large quantities of material from embryos, larvae, pupae and adult flies, in a synchronized way, at a low economic cost. A major strategy for propagating large numbers of flies is the use of a fly population cage. This useful and common tool in the Drososphila community is an efficient way to regularly produce milligrams to tens of grams of embryos, depending on uniformity of developmental stage desired. While a population cage can be time consuming to set up, maintaining a cage over months takes much less time and enables rapid collection of biological material in a short period. This paper describes a detailed and flexible protocol for the maintenance of a Drosophila melanogaster population cage, starting with 1.5 g of harvested material from the previous cycle.

  17. MicroRNA function in Drosophila melanogaster.

    Science.gov (United States)

    Carthew, Richard W; Agbu, Pamela; Giri, Ritika

    2017-05-01

    Over the last decade, microRNAs have emerged as critical regulators in the expression and function of animal genomes. This review article discusses the relationship between microRNA-mediated regulation and the biology of the fruit fly Drosophila melanogaster. We focus on the roles that microRNAs play in tissue growth, germ cell development, hormone action, and the development and activity of the central nervous system. We also discuss the ways in which microRNAs affect robustness. Many gene regulatory networks are robust; they are relatively insensitive to the precise values of reaction constants and concentrations of molecules acting within the networks. MicroRNAs involved in robustness appear to be nonessential under uniform conditions used in conventional laboratory experiments. However, the robust functions of microRNAs can be revealed when environmental or genetic variation otherwise has an impact on developmental outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Exquisite light sensitivity of Drosophila melanogaster cryptochrome.

    Directory of Open Access Journals (Sweden)

    Pooja Vinayak

    Full Text Available Drosophila melanogaster shows exquisite light sensitivity for modulation of circadian functions in vivo, yet the activities of the Drosophila circadian photopigment cryptochrome (CRY have only been observed at high light levels. We studied intensity/duration parameters for light pulse induced circadian phase shifts under dim light conditions in vivo. Flies show far greater light sensitivity than previously appreciated, and show a surprising sensitivity increase with pulse duration, implying a process of photic integration active up to at least 6 hours. The CRY target timeless (TIM shows dim light dependent degradation in circadian pacemaker neurons that parallels phase shift amplitude, indicating that integration occurs at this step, with the strongest effect in a single identified pacemaker neuron. Our findings indicate that CRY compensates for limited light sensitivity in vivo by photon integration over extraordinarily long times, and point to select circadian pacemaker neurons as having important roles.

  19. The developmental transcriptome of Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    University of Connecticut; Graveley, Brenton R.; Brooks, Angela N.; Carlson, Joseph W.; Duff, Michael O.; Landolin, Jane M.; Yang, Li; Artieri, Carlo G.; van Baren, Marijke J.; Boley, Nathan; Booth, Benjamin W.; Brown, James B.; Cherbas, Lucy; Davis, Carrie A.; Dobin, Alex; Li, Renhua; Lin, Wei; Malone, John H.; Mattiuzzo, Nicolas R.; Miller, David; Sturgill, David; Tuch, Brian B.; Zaleski, Chris; Zhang, Dayu; Blanchette, Marco; Dudoit, Sandrine; Eads, Brian; Green, Richard E.; Hammonds, Ann; Jiang, Lichun; Kapranov, Phil; Langton, Laura; Perrimon, Norbert; Sandler, Jeremy E.; Wan, Kenneth H.; Willingham, Aarron; Zhang, Yu; Zou, Yi; Andrews, Justen; Bicke, Peter J.; Brenner, Steven E.; Brent, Michael R.; Cherbas, Peter; Gingeras, Thomas R.; Hoskins, Roger A.; Kaufman, Thomas C.; Oliver, Brian; Celniker, Susan E.

    2010-12-02

    Drosophila melanogaster is one of the most well studied genetic model organisms; nonetheless, its genome still contains unannotated coding and non-coding genes, transcripts, exons and RNA editing sites. Full discovery and annotation are pre-requisites for understanding how the regulation of transcription, splicing and RNA editing directs the development of this complex organism. Here we used RNA-Seq, tiling microarrays and cDNA sequencing to explore the transcriptome in 30 distinct developmental stages. We identified 111,195 new elements, including thousands of genes, coding and non-coding transcripts, exons, splicing and editing events, and inferred protein isoforms that previously eluded discovery using established experimental, prediction and conservation-based approaches. These data substantially expand the number of known transcribed elements in the Drosophila genome and provide a high-resolution view of transcriptome dynamics throughout development. Drosophila melanogaster is an important non-mammalian model system that has had a critical role in basic biological discoveries, such as identifying chromosomes as the carriers of genetic information and uncovering the role of genes in development. Because it shares a substantial genic content with humans, Drosophila is increasingly used as a translational model for human development, homeostasis and disease. High-quality maps are needed for all functional genomic elements. Previous studies demonstrated that a rich collection of genes is deployed during the life cycle of the fly. Although expression profiling using microarrays has revealed the expression of, 13,000 annotated genes, it is difficult to map splice junctions and individual base modifications generated by RNA editing using such approaches. Single-base resolution is essential to define precisely the elements that comprise the Drosophila transcriptome. Estimates of the number of transcript isoforms are less accurate than estimates of the number of genes

  20. Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss

    Science.gov (United States)

    2013-09-01

    Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT : Bone loss that results from age- related and post- menopausal osteoporosis , and...5 References……………………………………………………………………………. 10 4 Introduction Osteoporosis , both age- related and post- menopausal ...a novel and highly innovative therapeutic approach to age- related osteoporosis . Body On July 27, 2012 we requested a 6 month extension without

  1. Therapeutic potential of eccentric exercises for age-related muscle atrophy

    OpenAIRE

    Lim, Jae-Young

    2016-01-01

    Recent studies have focused on evidence-based interventions to prevent mobility decline and enhance physical performance in older adults. Several modalities, in addition to traditional strengthening programs, have been designed to manage age-related functional decline more effectively. In this study, we reviewed the current relevant literatures to assess the therapeutic potential of eccentric exercises for age-related muscle atrophy (sarcopenia). Age-related changes in human skeletal muscle, ...

  2. The role of education and verbal abilities in altering the effect of age-related gray matter differences on cognition.

    Science.gov (United States)

    Steffener, Jason; Barulli, Daniel; Habeck, Christian; O'Shea, Deirdre; Razlighi, Qolamreza; Stern, Yaakov

    2014-01-01

    Evidence suggests that individual variability in lifetime exposures influences how cognitive performance changes with advancing age. Brain maintenance and cognitive reserve are theories meant to account for preserved performance despite advancing age. These theories differ in their causal mechanisms. Brain maintenance predicts more advantageous lifetime exposures will reduce age-related neural differences. Cognitive reserve predicts that lifetime exposures will not directly reduce these differences but minimize their impact on cognitive performance. The present work used moderated-mediation modeling to investigate the contributions of these mechanisms at explaining variability in cognitive performance among a group of 39 healthy younger (mean age (standard deviation) 25.9 (2.92) and 45 healthy older adults (65.2 (2.79)). Cognitive scores were computed using composite measures from three separate domains (speed of processing, fluid reasoning, and memory), while their lifetime exposures were estimated using education and verbal IQ measures. T1-weighted MR images were used to measure cortical thickness and subcortical volumes. Results suggest a stronger role for cognitive reserve mechanisms in explaining age-related cognitive variability: even with age-related reduced gray matter, individuals with greater lifetime exposures could perform better given their quantity of brain measures.

  3. The role of education and verbal abilities in altering the effect of age-related gray matter differences on cognition.

    Directory of Open Access Journals (Sweden)

    Jason Steffener

    Full Text Available Evidence suggests that individual variability in lifetime exposures influences how cognitive performance changes with advancing age. Brain maintenance and cognitive reserve are theories meant to account for preserved performance despite advancing age. These theories differ in their causal mechanisms. Brain maintenance predicts more advantageous lifetime exposures will reduce age-related neural differences. Cognitive reserve predicts that lifetime exposures will not directly reduce these differences but minimize their impact on cognitive performance. The present work used moderated-mediation modeling to investigate the contributions of these mechanisms at explaining variability in cognitive performance among a group of 39 healthy younger (mean age (standard deviation 25.9 (2.92 and 45 healthy older adults (65.2 (2.79. Cognitive scores were computed using composite measures from three separate domains (speed of processing, fluid reasoning, and memory, while their lifetime exposures were estimated using education and verbal IQ measures. T1-weighted MR images were used to measure cortical thickness and subcortical volumes. Results suggest a stronger role for cognitive reserve mechanisms in explaining age-related cognitive variability: even with age-related reduced gray matter, individuals with greater lifetime exposures could perform better given their quantity of brain measures.

  4. Dietary and behavioral interventions protect against age related activation of caspase cascades in the canine brain.

    Directory of Open Access Journals (Sweden)

    Shikha Snigdha

    Full Text Available Lifestyle interventions such as diet, exercise, and cognitive training represent a quietly emerging revolution in the modern approach to counteracting age-related declines in brain health. Previous studies in our laboratory have shown that long-term dietary supplementation with antioxidants and mitochondrial cofactors (AOX or behavioral enrichment with social, cognitive, and exercise components (ENR, can effectively improve cognitive performance and reduce brain pathology of aged canines, including oxidative damage and Aβ accumulation. In this study, we build on and extend our previous findings by investigating if the interventions reduce caspase activation and ceramide accumulation in the aged frontal cortex, since caspase activation and ceramide accumulation are common convergence points for oxidative damage and Aβ, among other factors associated with the aged and AD brain. Aged beagles were placed into one of four treatment groups: CON--control environment/control diet, AOX--control environment/antioxidant diet, ENR--enriched environment/control diet, AOX/ENR--enriched environment/antioxidant diet for 2.8 years. Following behavioral testing, brains were removed and frontal cortices were analyzed to monitor levels of active caspase 3, active caspase 9 and their respective cleavage products such as tau and semaphorin7a, and ceramides. Our results show that levels of activated caspase-3 were reduced by ENR and AOX interventions with the largest reduction occurring with combined AOX/ENR group. Further, reductions in caspase-3 correlated with reduced errors in a reversal learning task, which depends on frontal cortex function. In addition, animals treated with an AOX arm showed reduced numbers of cells expressing active caspase 9 or its cleavage product semaphorin 7A, while ENR (but not AOX reduced ceramide levels. Overall, these data demonstrate that lifestyle interventions curtail activation of pro-degenerative pathways to improve cellular

  5. Dietary and behavioral interventions protect against age related activation of caspase cascades in the canine brain.

    Science.gov (United States)

    Snigdha, Shikha; Berchtold, Nicole; Astarita, Giuseppe; Saing, Tommy; Piomelli, Daniele; Cotman, Carl W

    2011-01-01

    Lifestyle interventions such as diet, exercise, and cognitive training represent a quietly emerging revolution in the modern approach to counteracting age-related declines in brain health. Previous studies in our laboratory have shown that long-term dietary supplementation with antioxidants and mitochondrial cofactors (AOX) or behavioral enrichment with social, cognitive, and exercise components (ENR), can effectively improve cognitive performance and reduce brain pathology of aged canines, including oxidative damage and Aβ accumulation. In this study, we build on and extend our previous findings by investigating if the interventions reduce caspase activation and ceramide accumulation in the aged frontal cortex, since caspase activation and ceramide accumulation are common convergence points for oxidative damage and Aβ, among other factors associated with the aged and AD brain. Aged beagles were placed into one of four treatment groups: CON--control environment/control diet, AOX--control environment/antioxidant diet, ENR--enriched environment/control diet, AOX/ENR--enriched environment/antioxidant diet for 2.8 years. Following behavioral testing, brains were removed and frontal cortices were analyzed to monitor levels of active caspase 3, active caspase 9 and their respective cleavage products such as tau and semaphorin7a, and ceramides. Our results show that levels of activated caspase-3 were reduced by ENR and AOX interventions with the largest reduction occurring with combined AOX/ENR group. Further, reductions in caspase-3 correlated with reduced errors in a reversal learning task, which depends on frontal cortex function. In addition, animals treated with an AOX arm showed reduced numbers of cells expressing active caspase 9 or its cleavage product semaphorin 7A, while ENR (but not AOX) reduced ceramide levels. Overall, these data demonstrate that lifestyle interventions curtail activation of pro-degenerative pathways to improve cellular health and are the

  6. Age-related synaptic loss of the medial olivocochlear efferent innervation

    Directory of Open Access Journals (Sweden)

    Schrader Angela

    2010-11-01

    Full Text Available Abstract Age-related functional decline of the nervous system is consistently observed, though cellular and molecular events responsible for this decline remain largely unknown. One of the most prevalent age-related functional declines is age-related hearing loss (presbycusis, a major cause of which is the loss of outer hair cells (OHCs and spiral ganglion neurons. Previous studies have also identified an age-related functional decline in the medial olivocochlear (MOC efferent system prior to age-related loss of OHCs. The present study evaluated the hypothesis that this functional decline of the MOC efferent system is due to age-related synaptic loss of the efferent innervation of the OHCs. To this end, we used a recently-identified transgenic mouse line in which the expression of yellow fluorescent protein (YFP, under the control of neuron-specific elements from the thy1 gene, permits the visualization of the synaptic connections between MOC efferent fibers and OHCs. In this model, there was a dramatic synaptic loss between the MOC efferent fibers and the OHCs in older mice. However, age-related loss of efferent synapses was independent of OHC status. These data demonstrate for the first time that age-related loss of efferent synapses may contribute to the functional decline of the MOC efferent system and that this synaptic loss is not necessary for age-related loss of OHCs.

  7. Eyewear Equipped with a Triaxial Accelerometer Detects Age-Related Changes in Ambulatory Activity

    Directory of Open Access Journals (Sweden)

    Shigeyuki Ikeda

    2017-11-01

    Full Text Available Aging is known as a risk factor for gait disorders, which lead to reduced quality of life. Gait disorders can potentially be a sign of a preclinical phase of neurological diseases. Therefore, routine monitoring of changes in ambulatory activity with age can lead to early detection of such disorders. JINS MEME is eyewear equipped with a triaxial accelerometer (mediolateral, anteroposterior, and vertical and capable of measuring acceleration signals during gait. To validate effectiveness of JINS MEME in routinely monitoring age-related changes in ambulatory activity, the present study tested three hypotheses: (1 the frequency of mediolateral body sway during gait increases with age, (2 the variability of gait speed (anteroposterior increases with age, and (3 the frequency of vertical body sway during gait increases with age. The present study included 118 subjects aged 25–69 years. The acceleration signals were measured by JINS MEME while each subject walked down a barrier-free 20-meter-long level corridor at a natural pace. Triaxial variances known for reflecting gait stability, were calculated from the acceleration signals during gait. An association between each of the triaxial variances and age was assessed by multiple linear robust regression analysis including sex as a nuisance covariate. We found significant positive correlations between the anteroposterior variance and age and between the vertical variance and age. The results supported our second and third hypotheses and raised an intriguing possibility that the triaxial accelerometer of JINS MEME is capable of detecting age-related changes in ambulatory activity.

  8. Heightened inflammasome activation is linked to age-related cognitive impairment in Fischer 344 rats

    Directory of Open Access Journals (Sweden)

    Mawhinney Lana J

    2011-12-01

    Full Text Available Abstract Background Members of the mammalian nucleotide binding domain, leucine-rich repeat (LRR-containing receptor (NLR family of proteins are key modulators of innate immunity regulating inflammation. Our previous work has shown that among the members of this family, NLRP1/NALP1, present in neurons, plays a crucial role in inflammasome formation and the production of the inflammatory cytokines interleukin (IL -1β and IL-18 after various types of central nervous system injury. Results We investigated whether age-related cognitive decline may involve a heightened inflammatory response associated with activation of the NLRP1 inflammasome in the hippocampus. Young (3 months and aged (18 months male Fischer 344 rats were tested in a spatial acquisition task via Morris water maze. Following behavioral testing, hippocampal lysates were assayed for expression of NLRP1 inflammasome components and inflammatory cytokines. Hippocampal lysates from aged rats showed significantly higher levels of NLRP1 inflammasome constituents, caspase-1, caspase-11, the purinergic receptor P2X7, pannexin-1 and X-linked inhibitor of apoptosis (XIAP than lysates from younger animals. Following treatment with probenecid, an inhibitor or pannexin-1, aged animals demonstrated reduction in inflammasome activation and improvement in spatial learning performance. Conclusions Our behavioral findings are consistent with increases in IL-1β and IL-18 that have been previously shown to correlate with spatial learning deficits. Probenecid reduced activated caspase-1 and ameliorated spatial learning deficits in aged rats. Thus, aging processes stimulate activation of the NLRP1 inflammasome and secretion of IL-1β and IL-18 that may contribute to age-related cognitive decline in the growing elderly population. Moreover, probenecid may be potentially useful as a therapy to improve cognitive outcomes in the aging population.

  9. Understanding age-related reductions in visual working memory capacity: examining the stages of change detection.

    Science.gov (United States)

    Ko, Philip C; Duda, Bryant; Hussey, Erin; Mason, Emily; Molitor, Robert J; Woodman, Geoffrey F; Ally, Brandon A

    2014-10-01

    Visual working memory (VWM) capacity is reduced in older adults. Research has shown age-related impairments to VWM encoding, but aging is likely to affect multiple stages of VWM. In the present study, we recorded the event-related potentials (ERPs) of younger and older adults during VWM maintenance and retrieval. We measured encoding-stage processing with the P1 component, maintenance-stage processing with the contralateral delay activity (CDA), and retrieval-stage processing by comparing the activity for old and new items (old-new effect). Older adults showed lower behavioral capacity estimates (K) than did younger adults, but surprisingly, their P1 components and CDAs were comparable to those of younger adults. This remarkable dissociation between neural activity and behavior in the older adults indicated that the P1 and CDA did not accurately assess their VWM capacity. However, the neural activity evoked during VWM retrieval yielded results that helped clarify the age-related differences. During retrieval, younger adults showed early old-new effects in frontal and occipital areas and a late central-parietal old-new effect, whereas older adults showed a late right-lateralized parietal old-new effect. The younger adults' early old-new effects strongly resembled an index of perceptual fluency, suggesting that perceptual implicit memory was activated. The activation of implicit memory could have facilitated the younger adults' behavior, and the lack of these early effects in older adults may suggest that they have much lower-resolution memory than do younger adults. From these data, we speculated that younger and older adults store the same number of items in VWM, but that younger adults store a higher-resolution representation than do older adults.

  10. Age-Related Differences in Lexical Access Relate to Speech Recognition in Noise

    Science.gov (United States)

    Carroll, Rebecca; Warzybok, Anna; Kollmeier, Birger; Ruigendijk, Esther

    2016-01-01

    Vocabulary size has been suggested as a useful measure of “verbal abilities” that correlates with speech recognition scores. Knowing more words is linked to better speech recognition. How vocabulary knowledge translates to general speech recognition mechanisms, how these mechanisms relate to offline speech recognition scores, and how they may be modulated by acoustical distortion or age, is less clear. Age-related differences in linguistic measures may predict age-related differences in speech recognition in noise performance. We hypothesized that speech recognition performance can be predicted by the efficiency of lexical access, which refers to the speed with which a given word can be searched and accessed relative to the size of the mental lexicon. We tested speech recognition in a clinical German sentence-in-noise test at two signal-to-noise ratios (SNRs), in 22 younger (18–35 years) and 22 older (60–78 years) listeners with normal hearing. We also assessed receptive vocabulary, lexical access time, verbal working memory, and hearing thresholds as measures of individual differences. Age group, SNR level, vocabulary size, and lexical access time were significant predictors of individual speech recognition scores, but working memory and hearing threshold were not. Interestingly, longer accessing times were correlated with better speech recognition scores. Hierarchical regression models for each subset of age group and SNR showed very similar patterns: the combination of vocabulary size and lexical access time contributed most to speech recognition performance; only for the younger group at the better SNR (yielding about 85% correct speech recognition) did vocabulary size alone predict performance. Our data suggest that successful speech recognition in noise is mainly modulated by the efficiency of lexical access. This suggests that older adults’ poorer performance in the speech recognition task may have arisen from reduced efficiency in lexical access

  11. Conditional ablation of the choroideremia gene causes age-related changes in mouse retinal pigment epithelium.

    Directory of Open Access Journals (Sweden)

    Silène T Wavre-Shapton

    Full Text Available The retinal pigment epithelium (RPE is a pigmented monolayer of cells lying between the photoreceptors and a layer of fenestrated capillaries, the choriocapillaris. Choroideremia (CHM is an X-linked progressive degeneration of these three layers caused by the loss of function of Rab Escort protein-1 (REP1. REP1 is involved in the prenylation of Rab proteins, key regulators of membrane trafficking. To study the pathological consequences of chronic disruption of membrane traffic in the RPE we used a cell type-specific knock-out mouse model of the disease, where the Chm/Rep1 gene is deleted only in pigmented cells (Chm(Flox, Tyr-Cre+. Transmission electron microscopy (TEM was used to quantitate the melanosome distribution in the RPE and immunofluorescent staining of rhodopsin was used to quantitate phagocytosed rod outer segments in retinal sections. The ultrastructure of the RPE and Bruch's membrane at different ages was characterised by TEM to analyse age-related changes occurring as a result of defects in membrane traffic pathways. Chm/Rep1 gene knockout in RPE cells resulted in reduced numbers of melanosomes in the apical processes and delayed phagosome degradation. In addition, the RPE accumulated pathological changes at 5-6 months of age similar to those observed in 2-year old controls. These included the intracellular accumulation of lipofuscin-containing deposits, disorganised basal infoldings and the extracellular accumulation of basal laminar and basal linear deposits. The phenotype of the Chm(Flox, Tyr-Cre+ mice suggests that loss of the Chm/Rep1 gene causes premature accumulation of features of aging in the RPE. Furthermore, the striking similarities between the present observations and some of the phenotypes reported in age-related macular degeneration (AMD suggest that membrane traffic defects may contribute to the pathogenesis of AMD.

  12. Prevention and treatment of age-related macular degeneration: an update for pharmacists.

    Science.gov (United States)

    Marshall, Leisa L; Roach, J Michael

    2013-11-01

    Review the current recommendations for the prevention and treatment of age-related macular degeneration (AMD). Articles indexed in PubMed (National Library of Medicine), the Cochrane Reviews and Trials, Dynamed, and Iowa Drug Information Service (IDIS) in the last 10 years using the key words macular degeneration, agerelated macular degeneration (AMD), AMD and treatment, AMD and prevention. Sixty-nine published papers were reviewed, and criteria supporting the primary objective were used to identify useful resources. The literature included practice guidelines, original research articles, review articles, product prescribing information, and supplement product information for the prevention and treatment of AMD. AMD is a leading cause of visual impairment in older adults. At present there is no cure for advanced AMD, but intravitreal vascular endothelial growth factor inhibitors minimize and even reverse vision loss in patients with AMD of the neovascular type. In the Age-Related Eye Disease Study (AREDS), participants with intermediate AMD who received a supplement combination of vitamins C and E, beta-carotene, and zinc had a greater delay in progression to advanced AMD than those participants who received a portion of these supplements. In the second AREDS, AREDS2, the addition of lutein + zeaxanthin, docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), or lutein + zeaxanthin and DHA + EPA to the complete AREDS formulation did not further reduce the risk of progression to advanced AMD. Subgroup analyses indicated that additional research with lutein + zeaxanthin supplementation is warranted as it was beneficial in participants with low dietary intake of lutein + zeaxanthin. A formulation without beta-carotene may be best for most patients, especially smokers or former smokers. Health care professionals will want to consider patient-specific information before recommending ocular health supplements.

  13. Basis for the Age-related Decline in Intestinal Mucosal Immunity

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    Douglas L. Schmucker

    2003-01-01

    Full Text Available The elderly are characterized by mucosal immunosenescence and high rates of morbidity and mortality associated with infectious diseases of the intestinal tract. Little is known about how the differentiation of immunoglobulin A (IgA plasma cells in Peyer's patches (PPs and their subsequent homing to the small intestinal lamina propria (LP is affected by aging. Quantitative immunohistochemical analyses demonstrated a 2-fold increase in the number of IgA+ cells in the PPs, coupled with significant declines in the numbers of IgA+ and antibody-positive cells in the intestinal LP of senescent rats compared to young adult animals. These data suggest that aging diminishes the emigration of IgA immunoblasts from these lymphoid aggregates, as well as their migration to the intestinal LP. Flow cytometry and lymphocyte adoptive transfer studies showed 3- to 4-fold age-related declines in the homing of antibody-containing cells and mesenteric lymph node lymphocytes to the small intestines of rhesus macaques and rats, respectively. The number of peripheral blood IgA immunoblasts expressing the homing molecule α4β7 declined 30% in senescent rats. This was accompanied by a >17% decrease in the areal density of LP blood vessels staining positive for the cell adhesion molecule MAdCAM-1. Cumulatively, declines in expression of these homing molecules constitute a substantial age-related diminution of IgA immunoblast homing potential. In vitro antibody secretion by LP plasma cells, i.e. antibody secreted per antibody-positive cell, remains unchanged as a function of donor age. Intestinal mucosal immunosenescence is a consequence of reduced homing of IgA plasma cells to the intestinal LP as a result of declines in homing molecule expression.

  14. Age-related differences in street-crossing safety before and after training of older pedestrians.

    Science.gov (United States)

    Dommes, Aurélie; Cavallo, Viola; Vienne, Fabrice; Aillerie, Isabelle

    2012-01-01

    International accident statistics indicate that elderly pedestrians make up an extremely vulnerable road-user group. Past research has shown that older adults make many unsafe street-crossing decisions and adopt insufficient safety margins, especially when vehicles are approaching at high speed. Apart from studies on road design and speed-limit countermeasures, there is surprisingly no road-safety research on behavior-based measures to improve older pedestrians' safety. In this line, the present study was aimed at (i) assessing the effectiveness of a training program for older pedestrians that combined behavioral and educational interventions, and (ii) examining whether and to what extent age-related differences in street-crossing safety could be reduced after training older adults. Twenty seniors were enrolled in a training program. Before, immediately after, and six months after training, street-crossing behavior was assessed using a simulated street-crossing task. Twenty younger participants performed the same simulated task to obtain a baseline measure. The results showed that the training produced significant short- and long-term benefits, due to a shifting of the decision criteria among the older participants towards more conservative judgments. When compared with the younger group, the older participants improved their behavior considerably so that significant differences in the mean safety-related indicators were no longer observed. However, the older participants' ability to take the oncoming car's speed into account did not improve. Even after training, and contrary to younger adults, older participants were found to make more and more unsafe decisions as the car's speed increased, putting them at a higher risk at high speeds. This finding may reflect age-related perceptual and cognitive difficulties that cannot be remedied by a behavioral or educational training method. The present findings underline that high speed is an important risk factor for

  15. Age-related increases in false recognition: the role of perceptual and conceptual similarity

    Science.gov (United States)

    Pidgeon, Laura M.; Morcom, Alexa M.

    2014-01-01

    Older adults (OAs) are more likely to falsely recognize novel events than young adults, and recent behavioral and neuroimaging evidence points to a reduced ability to distinguish overlapping information due to decline in hippocampal pattern separation. However, other data suggest a critical role for semantic similarity. Koutstaal et al. [(2003) false recognition of abstract vs. common objects in older and younger adults: testing the semantic categorization account, J. Exp. Psychol. Learn. 29, 499–510] reported that OAs were only vulnerable to false recognition of items with pre-existing semantic representations. We replicated Koutstaal et al.’s (2003) second experiment and examined the influence of independently rated perceptual and conceptual similarity between stimuli and lures. At study, young and OAs judged the pleasantness of pictures of abstract (unfamiliar) and concrete (familiar) items, followed by a surprise recognition test including studied items, similar lures, and novel unrelated items. Experiment 1 used dichotomous “old/new” responses at test, while in Experiment 2 participants were also asked to judge lures as “similar,” to increase explicit demands on pattern separation. In both experiments, OAs showed a greater increase in false recognition for concrete than abstract items relative to the young, replicating Koutstaal et al.’s (2003) findings. However, unlike in the earlier study, there was also an age-related increase in false recognition of abstract lures when multiple similar images had been studied. In line with pattern separation accounts of false recognition, OAs were more likely to misclassify concrete lures with high and moderate, but not low degrees of rated similarity to studied items. Results are consistent with the view that OAs are particularly susceptible to semantic interference in recognition memory, and with the possibility that this reflects age-related decline in pattern separation. PMID:25368576

  16. Age-Related Deterioration of Perineuronal Nets in the Primary Auditory Cortex of Mice

    Directory of Open Access Journals (Sweden)

    Dustin H Brewton

    2016-11-01

    Full Text Available Age-related changes in inhibitory neurotransmission in sensory cortex may underlie deficits in sensory function. Perineuronal nets (PNNs are extracellular matrix components that ensheath some inhibitory neurons, particularly parvalbumin positive (PV+ interneurons. PNNs may protect PV+ cells from oxidative stress and help establish their rapid spiking properties. Although PNN expression has been well characterized during development, possible changes in aging sensory cortex have not been investigated. Here we tested the hypothesis that PNN+, PV+ and PV/PNN co-localized cell densities decline with age in the primary auditory cortex (A1. This hypothesis was tested using immunohistochemistry in two strains of mice (C57BL/6 and CBA/CaJ with different susceptibility to age-related hearing loss and at three different age ranges (1-3, 6-8 and 14-24 months old. We report that PNN+ and PV/PNN co-localized cell densities decline significantly with age in A1 in both mouse strains. In the PNN+ cells that remain in the old group, the intensity of PNN staining is reduced in the C57 strain, but not the CBA strain. PV+ cell density also declines only in the C57, but not the CBA, mouse suggesting a potential exacerbation of age-effects by hearing loss in the PV/PNN system. Taken together, these data suggest that PNN deterioration may be a key component of altered inhibition in the aging sensory cortex, that may lead to altered synaptic function, susceptibility to oxidative stress and processing deficits.

  17. The controversy over the association between statins use and progression of age-related macular degeneration: a mini review

    Directory of Open Access Journals (Sweden)

    Vasileios Peponis

    2010-07-01

    Full Text Available Vasileios Peponis1, Spyridon E Chalkiadakis1, Stefanos Bonovas2,3, Nikolaos M Sitaras21Athens Eye Hospital, 2nd Eye Clinic, Athens, Greece; 2Department of Pharmacology, School of Medicine, University of Athens, Greece; 3Center for Diseases Control and Prevention, Athens, GreeceObjective: Age-related macular degeneration (AMD is the leading cause of blindness in ¬western societies. Statins comprise a class of pharmacological agents that reduce plasma cholesterol levels, and have been shown to prevent progression of atherosclerosis and reduce cardiovascular mortality. The relationship between these medications and AMD has been evaluated in several recent studies. Herein, we examine the current evidence for an association between statin use and risk of AMD.Methods: Literature database search (Medline, Scopus, and Science Citation Index Expanded for articles published up to March 2010, using particular search terms.Results: From the current evidence available, it is not safe to conclude upon the assumption of a protective effect of statins against age-related maculopathy and AMD.Conclusion: There is a need for large scale prospective studies with a long follow-up period and accurate assessment of AMD to further explore this matter.Keywords: age-related macular degeneration (AMD, blindness, statin use, controversy

  18. fMRI and sleep correlates of the age-related impairment in motor memory consolidation.

    Science.gov (United States)

    Fogel, Stuart M; Albouy, Genevieve; Vien, Catherine; Popovicci, Romana; King, Bradley R; Hoge, Rick; Jbabdi, Saad; Benali, Habib; Karni, Avi; Maquet, Pierre; Carrier, Julie; Doyon, Julien

    2014-08-01

    Behavioral studies indicate that older adults exhibit normal motor sequence learning (MSL), but paradoxically, show impaired consolidation of the new memory trace. However, the neural and physiological mechanisms underlying this impairment are entirely unknown. Here, we sought to identify, through functional magnetic resonance imaging during MSL and electroencephalographic (EEG) recordings during daytime sleep, the functional correlates and physiological characteristics of this age-related motor memory deficit. As predicted, older subjects did not exhibit sleep-dependent gains in performance (i.e., behavioral changes that reflect consolidation) and had reduced sleep spindles compared with young subjects. Brain imaging analyses also revealed that changes in activity across the retention interval in the putamen and related brain regions were associated with sleep spindles. This change in striatal activity was increased in young subjects, but reduced by comparison in older subjects. These findings suggest that the deficit in sleep-dependent motor memory consolidation in elderly individuals is related to a reduction in sleep spindle oscillations and to an associated decrease of activity in the cortico-striatal network. Copyright © 2013 Wiley Periodicals, Inc.

  19. Role of flicker perimetry in predicting onset of late-stage age-related macular degeneration.

    Science.gov (United States)

    Luu, Chi D; Dimitrov, Peter N; Robman, Luba; Varsamidis, Mary; Makeyeva, Galina; Aung, Khin-Zaw; Vingrys, Algis J; Guymer, Robyn H

    2012-06-01

    To investigate the longitudinal changes in flicker perimetry in patients with age-related macular degeneration (AMD) as the condition progresses from early AMD to geographic atrophy (GA) or choroidal neovascularization (CNV). Patients with AMD and control subjects were recruited from a longitudinal study of retinal function in early AMD consisting of 187 participants. Only those who completed at least 4 consecutive, 6-monthly flicker perimetry tests were selected for this study. Study groups consisted of everyone who went on to develop GA (n = 16) or CNV (n = 5), controls (n = 24), and the high-risk, early- AMD participants whose eyes did not progress to GA or CNV (drusen >125 μm; n = 18). The flicker sensitivity was determined, and its rate of change during the 18 months before the clinical detection of late AMD was calculated. Eyes that went on to develop GA or CNV had a significantly reduced mean (SD) flicker sensitivity in the months before clinical detection of GA (15.8 [5.6] dB) or CNV (19.1 [3.8] dB) compared with control eyes (22.9 [3.0] dB) (P flicker sensitivity was significantly increased in GA eyes (-0.07 dB/mo) (P Flicker sensitivity is reduced in eyes that go on to develop late AMD. The rate of change in flicker sensitivities over time was particularly useful in predicting eyes and areas within the eye that subsequently develop GA.

  20. Age-related changes in motor cortical properties and voluntary activation of skeletal muscle.

    Science.gov (United States)

    Clark, Brian C; Taylor, Janet L

    2011-12-01

    Aging is associated with dramatic reductions in muscle strength and motor control, and many of these agerelated changes in muscle function result from adaptations in the central nervous system. Aging is associated with widespread qualitative and quantitative changes of the motor cortex. For example, advancing age has been suggested to result in cortical atrophy, reduced cortical excitability, reduced cortical plasticity, as well as neurochemical abnormalities.The associated functional effects of these changes likely influence numerous aspects of muscle performance such as muscle strength and motor control. For example, there is evidence to suggest that the muscle weakness associated with aging is partially due to impairments in the nervous system's ability to fully activate motor neurons- particularly in the larger proximal muscle groups. In this review article we discuss age-related changes in the motor cortex, as well as the abilityor lack thereof- of older adults to voluntarily activate skeletal muscle. We also provide perspectives on scientific and clinical questions that need to be addressed in the near future.

  1. Mitochondrial-targeted plastoquinone derivatives. Effect on senescence and acute age-related pathologies.

    Science.gov (United States)

    Skulachev, M V; Antonenko, Y N; Anisimov, V N; Chernyak, B V; Cherepanov, D A; Chistyakov, V A; Egorov, M V; Kolosova, N G; Korshunova, G A; Lyamzaev, K G; Plotnikov, E Y; Roginsky, V A; Savchenko, A Y; Severina, I I; Severin, F F; Shkurat, T P; Tashlitsky, V N; Shidlovsky, K M; Vyssokikh, M Y; Zamyatnin, A A; Zorov, D B; Skulachev, V P

    2011-06-01

    Plastoquinone, a very effective electron carrier and antioxidant of chloroplasts, was conjugated with decyltriphenylphosphonium to obtain a cation easily penetrating through membranes. This cation, called SkQ1, is specifically targeted to mitochondria by electrophoresis in the electric field formed by the mitochondrial respiratory chain. The respiratory chain also regenerates reduced SkQ1H(2) from its oxidized form that appears as a result of the antioxidant activity of SkQ1H(2). SkQ1H(2) prevents oxidation of cardiolipin, a mitochondrial phospholipid that is especially sensitive to attack by reactive oxygen species (ROS). In cell cultures, SkQ1 and its analog plastoquinonyl decylrhodamine 19 (SkQR1) arrest H(2)O(2)-induced apoptosis. When tested in vivo, SkQs (i) prolong the lifespan of fungi, crustaceans, insects, fish, and mice, (ii) suppress appearance of a large number of traits typical for age-related senescence (cataract, retinopathies, achromotrichia, osteoporosis, lordokyphosis, decline of the immune system, myeloid shift of blood cells, activation of apoptosis, induction of β-galactosidase, phosphorylation of H2AX histones, etc.) and (iii) lower tissue damage and save the lives of young animals after treatments resulting in kidney ischemia, rhabdomyolysis, heart attack, arrhythmia, and stroke. We suggest that the SkQs reduce mitochondrial ROS and, as a consequence, inhibit mitochondria-mediated apoptosis, an obligatory step of execution of programs responsible for both senescence and fast "biochemical suicide" of an organism after a severe metabolic crisis.

  2. The relationship of major American dietary patterns to age-related macular degeneration

    Science.gov (United States)

    We hypothesized that major American dietary patterns are associated with age-related macular degeneration (AMD) risk. This was a cross-sectional study with 8,103 eyes from 4,088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into control (n=2,739), early ...

  3. Incidence and progression rates of age-related maculopathy: the Rotterdam Study

    NARCIS (Netherlands)

    J.J.M. Willemse-Assink (Jacqueline); R. van Leeuwen (Redmer); R.C.W. Wolfs (Roger); J.R. Vingerling (Hans); Th. Stijnen (Theo); P.T.V.M. de Jong (Paulus); C.C.W. Klaver (Caroline); A. Hofman (Albert)

    2001-01-01

    textabstractPURPOSE: To describe the incidence rate of age-related macular degeneration (AMD) and the progression rates of early stages of age-related maculopathy (ARM), and to study the hierarchy of fundus features that determine progression. METHODS: A group of 4953 subjects

  4. Vitamin D deficiency in neovascular versus nonneovascular age-related macular degeneration.

    Science.gov (United States)

    Itty, Sujit; Day, Shelley; Lyles, Kenneth W; Stinnett, Sandra S; Vajzovic, Lejla M; Mruthyunjaya, Prithvi

    2014-09-01

    To compare 25-hydroxyvitamin D (25OHD) levels in patients with neovascular age-related macular degeneration (NVAMD) with patients with nonneovascular age-related macular degeneration and control patients. Medical records of all patients diagnosed with age-related macular degeneration and tested for serum 25OHD level at a single medical center were reviewed. Control patients were selected from patients diagnosed with pseudophakia but without age-related macular degeneration. The lowest 25OHD level available for each patient was recorded. Two hundred sixteen patients with nonneovascular age-related macular degeneration, 146 with NVAMD, and 100 non-age-related macular degeneration control patients were included. The levels of 25OHD (mean ± SD) were significantly lower in NVAMD patients (26.1 ± 14.4 ng/mL) versus nonneovascular age-related macular degeneration (31.5 ± 18.2 ng/mL, P = 0.003) and control (29.4 ± 10.1 ng/mL, P = 0.049) patients. The prevalence of vitamin D insufficiency (age-related macular degeneration. Mean 25OHD levels were lower and vitamin D deficiency was more prevalent in NVAMD patients. These associations suggest that further research is necessary regarding vitamin D deficiency as a potentially modifiable risk factor for the development of NVAMD.

  5. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration

    DEFF Research Database (Denmark)

    Larsen, Michael; Schmidt-Erfurth, Ursula; Lanzetta, Paolo

    2012-01-01

    To compare the efficacy and safety of same-day verteporfin photodynamic therapy (PDT) and intravitreal ranibizumab combination treatment versus ranibizumab monotherapy in neovascular age-related macular degeneration.......To compare the efficacy and safety of same-day verteporfin photodynamic therapy (PDT) and intravitreal ranibizumab combination treatment versus ranibizumab monotherapy in neovascular age-related macular degeneration....

  6. Subfoveal fibrosis in eyes with neovascular age-related macular degeneration treated with intravitreal ranibizumab

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi; Lund-Andersen, Henrik; Sander, Birgit

    2013-01-01

    To assess baseline and follow-up characteristics of choroidal neovascularization (CNV) lesions in age-related macular degeneration in relation to the development of subfoveal subretinal fibrosis.......To assess baseline and follow-up characteristics of choroidal neovascularization (CNV) lesions in age-related macular degeneration in relation to the development of subfoveal subretinal fibrosis....

  7. Age-related attitudes: the influence on relationships and performance at work

    NARCIS (Netherlands)

    Dr. Franz Josef Gellert; R. Schalk

    2012-01-01

    Purpose: – This paper aims to examine the influence of age and age-related attitudes on relationship factors. In addition, it seeks to assess how both factors affect care service work performance. Design/methodology/approach: – The paper explores the influence of age and age-related attitudes on the

  8. The cuticular nature of corneal lenses in Drosophila melanogaster.

    Science.gov (United States)

    Stahl, Aaron L; Charlton-Perkins, Mark; Buschbeck, Elke K; Cook, Tiffany A

    2017-07-01

    The dioptric visual system relies on precisely focusing lenses that project light onto a neural retina. While the proteins that constitute the lenses of many vertebrates are relatively well characterized, less is known about the proteins that constitute invertebrate lenses, especially the lens facets in insect compound eyes. To address this question, we used mass spectrophotometry to define the major proteins that comprise the corneal lenses from the adult Drosophila melanogaster compound eye. This led to the identification of four cuticular proteins: two previously identified lens proteins, drosocrystallin and retinin, and two newly identified proteins, Cpr66D and Cpr72Ec. To determine which ommatidial cells contribute each of these proteins to the lens, we conducted in situ hybridization at 50% pupal development, a key age for lens secretion. Our results confirm previous reports that drosocrystallin and retinin are expressed in the two primary corneagenous cells-cone cells and primary pigment cells. Cpr72Ec and Cpr66D, on the other hand, are more highly expressed in higher order interommatidial pigment cells. These data suggest that the complementary expression of cuticular proteins give rise to the center vs periphery of the corneal lens facet, possibly facilitating a refractive gradient that is known to reduce spherical aberration. Moreover, these studies provide a framework for future studies aimed at understanding the cuticular basis of corneal lens function in holometabolous insect eyes.

  9. Obp56h Modulates Mating Behavior in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    John R. Shorter

    2016-10-01

    Full Text Available Social interactions in insects are driven by conspecific chemical signals that are detected via olfactory and gustatory neurons. Odorant binding proteins (Obps transport volatile odorants to chemosensory receptors, but their effects on behaviors remain poorly characterized. Here, we report that RNAi knockdown of Obp56h gene expression in Drosophila melanogaster enhances mating behavior by reducing courtship latency. The change in mating behavior that results from inhibition of Obp56h expression is accompanied by significant alterations in cuticular hydrocarbon (CHC composition, including reduction in 5-tricosene (5-T, an inhibitory sex pheromone produced by males that increases copulation latency during courtship. Whole genome RNA sequencing confirms that expression of Obp56h is virtually abolished in Drosophila heads. Inhibition of Obp56h expression also affects expression of other chemoreception genes, including upregulation of lush in both sexes and Obp83ef in females, and reduction in expression of Obp19b and Or19b in males. In addition, several genes associated with lipid metabolism, which underlies the production of cuticular hydrocarbons, show altered transcript abundances. Our data show that modulation of mating behavior through reduction of Obp56h is accompanied by altered cuticular hydrocarbon profiles and implicate 5-T as a possible ligand for Obp56h.

  10. Antioxidant content and cytological examination of aqueous fluid from patients with age-related cataracts at different stages.

    Science.gov (United States)

    Wang, X; Sun, J; Dang, G F; Gao, Y; Duan, L; Wu, X Y

    2015-06-11

    We investigated the antioxidant content and conducted a cytological examination of the aqueous fluid and lenses of patients with age-related cataracts at different stages. The levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) in the aqueous fluid and lenses were determined by the xanthine oxidase method, the colorimetric method, and the improved reduced glutathione (GSH) depletion method, respectively. SOD, CAT, and GSH-PX content in the aqueous fluid and lenses decreased significantly with increasing lenticular nucleus hardness grading. However, the number of white blood cells, neutrophils, monocytes, lymphocytes, and eosinophils did not vary significantly with varying lenticular nucleus hardness. Antioxidant content examination is an important quantitative indicator for clinical diagnosis and treatment of age-related cataracts. Antioxidant content in the aqueous fluid and lenses decreased significantly with increasing lenticular nucleus hardness grading. Lenses at hardness level V had the lowest content of antioxidants.

  11. Visual Detection of Speckles in the Fish Xenotoca variata by the Predatory Snake Thamnophis melanogaster in Water of Different Turbidity

    OpenAIRE

    Manjarrez, Javier; Rivas-Gonz?lez, Eric; Venegas-Barrera, Crystian S.; Moyaho, Alejandro

    2015-01-01

    Semi-aquatic snakes integrate visual and chemical stimuli, and prey detection and capture success are therefore linked to the display of visual predatory behavior. The snake Thamnophis melanogaster responds preferentially to individuals of the fish Xenotoca variata with a greater number of bright, colorful spots (lateral speckles) compared with those with a smaller number; however, water turbidity can reduce underwater visibility and effect the vulnerability of fish. In this study, we tested ...

  12. [The genetic variability of complement system in pathogenesis of age-related macular degeneration].

    Science.gov (United States)

    Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Dziedzina, Sylwia; Sanak, Marek

    2015-01-01

    Age-related macular degeneration is the leading cause of irreversible central vision impairment in people aged over 50 in developed countries. Age-related macular degeneration is a complex disease derived from environmental, immune and genetic factors. The complement pathway has been implicated in the pathogenesis of many diseases. Recently, variants in several genes, such as complement H (CFH), complement factor B (CFB), complement 2 (C2), and complement 3 (C3), encoding complement pathway proteins, have been identified as associated with age-related macular degeneration. However, the associations between these genes and age-related macular degeneration varied due to genetic variation within populations and various ethnics groups. The strongest association was found between the age-related macular degeneration and SNP Y402H rs 1061170 variant of CFH gene, which is present in 30% to 50% of age-related macular degeneration patients in Caucasian population and which is a risk factor for the development of age-related macular degeneration. Cohort studies showed that polymorphism Arg102Gly (SNP rs 2230199) of C3 protein could serve as a high-risk genetic marker for the development of age-related macular degeneration. Other rare variants of C3 (Lys155Gln, Lys65Gln, Arg735Trp, Ser1619Arg), may also be associated with a high incidence of age-related macular degeneration in some ethnic groups. A protective haplotype of variants E318D and IVS10 in the C2 gene as well as L9H and R320 in the BF were associated with age-related macular degeneration but only in Caucasians. The genetic findings in age-related macular degeneration patients stress the importance of detailed phenotyping to identify age-related macular degeneration subtypes, which may be associated with the presence of different polymorphisms and various environmental risk factors in any population. Further studies may be helpful to improve the effectiveness of prophylaxis and therapeutic options in age-related

  13. Sexual selection and immune function in Drosophila melanogaster.

    Science.gov (United States)

    McKean, Kurt A; Nunney, Leonard

    2008-02-01

    The evolution of immune function depends not only on variation in genes contributing directly to the immune response, but also on genetic variation in other traits indirectly affecting immunocompetence. In particular, sexual selection is predicted to trade-off with immunocompetence because the extra investment of resources needed to increase sexual competitiveness reduces investment in immune function. Additional possible immunological consequences of intensifying sexual selection include an exaggeration of immunological sexual dimorphism, and the reduction of condition-dependent immunological costs due to selection of 'good genes' (the immunocompetence handicap hypothesis, ICHH). We tested for these evolutionary possibilities by increasing sexual selection in laboratory populations of Drosophila melanogaster for 58 generations by reestablishing a male-biased sex ratio at the start of each generation. Sexually selected flies were larger, took longer to develop, and the males were more sexually competitive than males from control (equal sex ratio) lines. We found support for the trade-off hypothesis: sexually selected males were found to have reduced immune function compared to control males. However, we found no evidence that sexual selection promoted immunological sexual dimorphism because females showed a similar reduction in immune function. We found no evidence of evolutionary changes in the condition-dependent expression of immunocompetence contrary to the expectations of the ICHH. Lastly, we compared males from the unselected base population that were either successful (IS) or unsuccessful (IU) in a competitive mating experiment. IS males showed reduced immune function relative to IU males, suggesting that patterns of phenotypic correlation largely mirror patterns of genetic correlation revealed by the selection experiment. Our results suggest increased disease susceptibility could be an important cost limiting increases in sexual competitiveness in

  14. Genomic Variation in Natural Populations of Drosophila melanogaster

    Science.gov (United States)

    Langley, Charles H.; Stevens, Kristian; Cardeno, Charis; Lee, Yuh Chwen G.; Schrider, Daniel R.; Pool, John E.; Langley, Sasha A.; Suarez, Charlyn; Corbett-Detig, Russell B.; Kolaczkowski, Bryan; Fang, Shu; Nista, Phillip M.; Holloway, Alisha K.; Kern, Andrew D.; Dewey, Colin N.; Song, Yun S.; Hahn, Matthew W.; Begun, David J.

    2012-01-01

    This report of independent genome sequences of two natural populations of Drosophila melanogaster (37 from North America and 6 from Africa) provides unique insight into forces shaping genomic polymorphism and divergence. Evidence of interactions between natural selection and genetic linkage is abundant not only in centromere- and telomere-proximal regions, but also throughout the euchromatic arms. Linkage disequilibrium, which decays within 1 kbp, exhibits a strong bias toward coupling of the more frequent alleles and provides a high-resolution map of recombination rate. The juxtaposition of population genetics statistics in small genomic windows with gene structures and chromatin states yields a rich, high-resolution annotation, including the following: (1) 5′- and 3′-UTRs are enriched for regions of reduced polymorphism relative to lineage-specific divergence; (2) exons overlap with windows of excess relative polymorphism; (3) epigenetic marks associated with active transcription initiation sites overlap with regions of reduced relative polymorphism and relatively reduced estimates of the rate of recombination; (4) the rate of adaptive nonsynonymous fixation increases with the rate of crossing over per base pair; and (5) both duplications and deletions are enriched near origins of replication and their density correlates negatively with the rate of crossing over. Available demographic models of X and autosome descent cannot account for the increased divergence on the X and loss of diversity associated with the out-of-Africa migration. Comparison of the variation among these genomes to variation among genomes from D. simulans suggests that many targets of directional selection are shared between these species. PMID:22673804

  15. Age-Related Reduction of Recovery Sleep and Arousal Threshold in Drosophila

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    Vienne, Julie; Spann, Ryanne; Guo, Fang; Rosbash, Michael

    2016-01-01

    Study Objectives: Physiological studies show that aging affects both sleep quality and quantity in humans, and sleep complaints increase with age. Along with knowledge about the negative effects of poor sleep on health, understanding the enigmatic relationship between sleep and aging is important. Because human sleep is similar to Drosophila (fruit fly) sleep in many ways, we addressed the effects of aging on sleep in this model organism. Methods: Baseline sleep was recorded in five different Drosophila genotypes raised at either 21°C or 25°C. The amount of sleep recovered was then investigated after a nighttime of sleep deprivation (12 h) and after chronic sleep deprivation (3 h every night for multiple nights). Finally, the effects of aging on arousal, namely, sensitivity to neuronal and mechanical stimuli, were studied. Results: We show that fly sleep is affected by age in a manner similar to that of humans and other mammals. Not only do older flies of several genotypes have more fragmented sleep and reduced total sleep time compared to young flies, but older flies also fail to recover as much sleep after sleep deprivation. This suggests either lower sleep homeostasis and/or a failure to properly recover sleep. Older flies also show a decreased arousal threshold, i.e., an increased response to neuronal and mechanical wake-promoting stimuli. The reduced threshold may either reflect or cause the reduced recovery sleep of older flies compared to young flies after sleep deprivation. Conclusions: Further studies are certainly needed, but we suggest that the lower homeostatic sleep drive of older flies causes their decreased arousal threshold. Citation: Vienne J, Spann R, Guo F, Rosbash M. Age-related reduction of recovery sleep and arousal threshold in Drosophila. SLEEP 2016;39(8):1613–1624. PMID:27306274

  16. Mechanical strain modulates age-related changes in the proliferation and differentiation of mouse adipose-derived stromal cells

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    Chiang Wen-Sheng

    2010-03-01

    Full Text Available Abstract Background Previous studies on the effects of aging in human and mouse mesenchymal stem cells suggest that a decline in the number and differentiation potential of stem cells may contribute to aging and aging-related diseases. In this report, we used stromal cells isolated from adipose tissue (ADSCs of young (8-10 weeks, adult (5 months, and old (21 months mice to test the hypothesis that mechanical loading modifies aging-related changes in the self-renewal and osteogenic and adipogenic differentiation potential of these cells. Results We show that aging significantly reduced the proliferation and increased the adipogenesis of ADSCs, while the osteogenic potential is not significantly reduced by aging. Mechanical loading (10% cyclic stretching, 0.5 Hz, 48 h increased the subsequent proliferation of ADSCs from mice of all ages. Although the number of osteogenic colonies with calcium deposition was increased in ADSCs subjected to pre-strain, it resulted from an increase in colony number rather than from an increase in osteogenic potential after strain. Pre-strain significantly reduced the number of oil droplets and the expression of adipogenic marker genes in adult and old ADSCs. Simultaneously subjecting ADSCs to mechanical loading and adipogenic induction resulted in a stronger inhibition of adipogenesis than that caused by pre-strain. The reduction of adipogenesis by mechanical strain was loading-magnitude dependent: loading with 2% strain only resulted in a partial inhibition, and loading with 0.5% strain could not inhibit adipogenesis in ADSCs. Conclusions We demonstrate that mechanical stretching counteracts the loss of self-renewal in aging ADSCs by enhancing their proliferation and, at the same time, reduces the heightened adipogenesis of old cells. These findings are important for the further study of stem cell control and treatment for a variety of aging related diseases.

  17. Gut-associated microbes of Drosophila melanogaster

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    Broderick, Nichole; Lemaitre, Bruno

    2012-01-01

    There is growing interest in using Drosophila melanogaster to elucidate mechanisms that underlie the complex relationships between a host and its microbiota. In addition to the many genetic resources and tools Drosophila provides, its associated microbiota is relatively simple (1–30 taxa), in contrast to the complex diversity associated with vertebrates (> 500 taxa). These attributes highlight the potential of this system to dissect the complex cellular and molecular interactions that occur between a host and its microbiota. In this review, we summarize what is known regarding the composition of gut-associated microbes of Drosophila and their impact on host physiology. We also discuss these interactions in the context of their natural history and ecology and describe some recent insights into mechanisms by which Drosophila and its gut microbiota interact. “Workers with Drosophila have been considered fortunate in that they deal with the first multicellular invertebrate to be cultured monoxenically (Delcourt and Guyenot, 1910); the first to be handled axenically on a semisynthetic diet (Guyenot, 1917); and the first to be grown on a defined diet (Schultz et al., 1946). This list of advantages is somewhat embarrassing, since it implies an interest in nutrition that, in reality, was only secondary. The very first studies were concerned with the reduction of variability in genetic experiments (Delcourt and Guyenot, 1910) and standardization of the nutritional environment.” -James Sang, 1959 Ann NY Acad 1 PMID:22572876

  18. The sexually antagonistic genes of Drosophila melanogaster.

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    Paolo Innocenti

    2010-03-01

    Full Text Available When selective pressures differ between males and females, the genes experiencing these conflicting evolutionary forces are said to be sexually antagonistic. Although the phenotypic effect of these genes has been documented in both wild and laboratory populations, their identity, number, and location remains unknown. Here, by combining data on sex-specific fitness and genome-wide transcript abundance in a quantitative genetic framework, we identified a group of candidate genes experiencing sexually antagonistic selection in the adult, which correspond to 8% of Drosophila melanogaster genes. As predicted, the X chromosome is enriched for these genes, but surprisingly they represent only a small proportion of the total number of sex-biased transcripts, indicating that the latter is a poor predictor of sexual antagonism. Furthermore, the majority of genes whose expression profiles showed a significant relationship with either male or female adult fitness are also sexually antagonistic. These results provide a first insight into the genetic basis of intralocus sexual conflict and indicate that genetic variation for fitness is dominated and maintained by sexual antagonism, potentially neutralizing any indirect genetic benefits of sexual selection.

  19. Ferritin Assembly in Enterocytes of Drosophila melanogaster

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    Abraham Rosas-Arellano

    2016-02-01

    Full Text Available Ferritins are protein nanocages that accumulate inside their cavity thousands of oxidized iron atoms bound to oxygen and phosphates. Both characteristic types of eukaryotic ferritin subunits are present in secreted ferritins from insects, but here dimers between Ferritin 1 Heavy Chain Homolog (Fer1HCH and Ferritin 2 Light Chain Homolog (Fer2LCH are further stabilized by disulfide-bridge in the 24-subunit complex. We addressed ferritin assembly and iron loading in vivo using novel transgenic strains of Drosophila melanogaster. We concentrated on the intestine, where the ferritin induction process can be controlled experimentally by dietary iron manipulation. We showed that the expression pattern of Fer2LCH-Gal4 lines recapitulated iron-dependent endogenous expression of the ferritin subunits and used these lines to drive expression from UAS-mCherry-Fer2LCH transgenes. We found that the Gal4-mediated induction of mCherry-Fer2LCH subunits was too slow to effectively introduce them into newly formed ferritin complexes. Endogenous Fer2LCH and Fer1HCH assembled and stored excess dietary iron, instead. In contrast, when flies were genetically manipulated to co-express Fer2LCH and mCherry-Fer2LCH simultaneously, both subunits were incorporated with Fer1HCH in iron-loaded ferritin complexes. Our study provides fresh evidence that, in insects, ferritin assembly and iron loading in vivo are tightly regulated.

  20. Characterization of Autophagic Responses in Drosophila melanogaster.

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    Xu, T; Kumar, S; Denton, D

    2017-01-01

    Drosophila is an excellent model system for studying autophagy during animal development due to the availability of genetic reagents and opportunity for in vivo cell biological analysis. The regulation and mechanism of autophagy are highly evolutionarily conserved and the role of autophagy has been characterized during various stages of Drosophila development as well as following starvation. Studies in Drosophila have revealed novel insights into the role of distinct components of the autophagy machinery. This chapter describes protocols for examining autophagy during Drosophila development. A crucial step in the induction of autophagy is the incorporation of Atg8a into the autophagosome. This can be measured as autophagic puncta using live fluorescent imaging, immunostaining, or immunoblot analysis of LC3/Atg8a processing. The level of autophagy can also be examined using other specific components of the autophagy pathway as markers detected by immunofluorescent imaging. Based on the distinct morphology of autophagy, it can also be examined by transmission electron microscopy. In addition, one of the advantages of using Drosophila as a model is the ability to undertake genetic analysis of individual components of the autophagy machinery. Current approaches that can be used to monitor autophagy, including the overall flux and individual steps in Drosophila melanogaster, will be discussed. © 2017 Elsevier Inc. All rights reserved.

  1. The Ran pathway in Drosophila melanogaster mitosis

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    James G Wakefield

    2015-11-01

    Full Text Available Over the last two decades, the small GTPase Ran has emerged as a central regulator of both mitosis and meiosis, particularly in the generation, maintenance and regulation of the microtubule (MT-based bipolar spindle. Ran-regulated pathways in mitosis bear many similarities to the well-characterized functions of Ran in nuclear transport and, as with transport, the majority of these mitotic effects are mediated through affecting the physical interaction between karyopherins and Spindle Assembly Factors (SAFs - a loose term describing proteins or protein complexes involved in spindle assembly through promoting nucleation, stabilization, and/or depolymerization of MTs, through anchoring MTs to specific structures such as centrosomes, chromatin or kinetochores, or through sliding MTs along each other to generate the force required to achieve bipolarity. As such, the Ran-mediated pathway represents a crucial functional module within the wider spindle assembly landscape. Research into mitosis using the model organism Drosophila melanogaster has contributed substantially to our understanding of centrosome and spindle function. However, in comparison to mammalian systems, very little is known about the contribution of Ran-mediated pathways in Drosophila mitosis. This article sets out to summarize our understanding of the roles of the Ran pathway components in Drosophila mitosis, focusing on the syncytial blastoderm embryo, arguing that, far from being superfluous, it can provide important insights into the conserved functions on Ran during spindle formation.

  2. The Effects of Royal Jelly on Fitness Traits and Gene Expression in Drosophila melanogaster.

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    John R Shorter

    Full Text Available Royal Jelly (RJ is a product made by honey bee workers and is required for queen differentiation and accompanying changes in queen body size, development time, lifespan and reproductive output relative to workers. Previous studies have reported similar changes in Drosophila melanogaster in response to RJ. Here, we quantified viability, development time, body size, productivity, lifespan and genome wide transcript abundance of D. melanogaster reared on standard culture medium supplemented with increasing concentrations of RJ. We found that lower concentrations of RJ do induce significant differences in body size in both sexes; higher concentrations reduce size, increase mortality, shorten lifespan and reduce productivity. Increased concentrations of RJ also consistently lengthened development time in both sexes. RJ is associated with changes in expression of 1,581 probe sets assessed using Affymetrix Drosophila 2.0 microarrays, which were enriched for genes associated with metabolism and amino acid degradation. The transcriptional changes are consistent with alterations in cellular processes to cope with excess nutrients provided by RJ, including biosynthesis and detoxification, which might contribute to accelerated senescence and reduced lifespan.

  3. Age-related changes in rostral basal forebrain cholinergic and GABAergic projection neurons: relationship with spatial impairment.

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    Bañuelos, Cristina; LaSarge, Candi L; McQuail, Joseph A; Hartman, John J; Gilbert, Ryan J; Ormerod, Brandi K; Bizon, Jennifer L

    2013-03-01

    Both cholinergic and GABAergic projections from the rostral basal forebrain contribute to hippocampal function and mnemonic abilities. While dysfunction of cholinergic neurons has been heavily implicated in age-related memory decline, significantly less is known regarding how age-related changes in codistributed GABAergic projection neurons contribute to a decline in hippocampal-dependent spatial learning. In the current study, confocal stereology was used to quantify cholinergic (choline acetyltransferase [ChAT] immunopositive) neurons, GABAergic projection (glutamic decarboxylase 67 [GAD67] immunopositive) neurons, and total (neuronal nuclei [NeuN] immunopositive) neurons in the rostral basal forebrain of young and aged rats that were first characterized on a spatial learning task. ChAT immunopositive neurons were significantly but modestly reduced in aged rats. Although ChAT immunopositive neuron number was strongly correlated with spatial learning abilities among young rats, the reduction of ChAT immunopositive neurons was not associated with impaired spatial learning in aged rats. In contrast, the number of GAD67 immunopositive neurons was robustly and selectively elevated in aged rats that exhibited impaired spatial learning. Interestingly, the total number of rostral basal forebrain neurons was comparable in young and aged rats, regardless of their cognitive status. These data demonstrate differential effects of age on phenotypically distinct rostral basal forebrain projection neurons, and implicate dysregulated cholinergic and GABAergic septohippocampal circuitry in age-related mnemonic decline. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Age-related functional changes and susceptibility to eccentric contraction-induced damage in skeletal muscle cell

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    Seung-Jun Choi

    2016-09-01

    Full Text Available Depending upon external loading conditions, skeletal muscles can either shorten, lengthen, or remain at a fixed length as they produce force. Fixed-end or isometric contractions stabilize joints and allow muscles to act as active struts during locomotion. Active muscles dissipate energy when they are lengthened by an external force that exceeds their current force producing capacity. These unaccustomed eccentric activities often lead to muscle weakness, soreness, and inflammation. During aging, the ability to produce force under these conditions is reduced and appears to be due to not only reductions in muscle mass but also to alterations in the basic mechanisms of contraction. These alterations include impairments in the excitation–contraction process, and the action of the cross-bridges. Also, it is well known that age-related skeletal muscle atrophy is characterized by a preferential atrophy of fast fibers, and increased susceptibility to fast muscle fiber when aged muscles are exposed to eccentric contraction followed by the impaired recovery process has been reported. Taken together, the selective loss of fast muscle fiber in aged muscle could be affected by eccentric-induced muscle damage, which has significant implication to identify the etiology of the age-related functional changes. Therefore, in this review the alteration of age-related muscle function and its impact to/of eccentric induced muscle damage and recovery will be addressed in detail.

  5. Age-related functional changes and susceptibility to eccentric contraction-induced damage in skeletal muscle cell.

    Science.gov (United States)

    Choi, Seung-Jun

    2016-09-01

    Depending upon external loading conditions, skeletal muscles can either shorten, lengthen, or remain at a fixed length as they produce force. Fixed-end or isometric contractions stabilize joints and allow muscles to act as active struts during locomotion. Active muscles dissipate energy when they are lengthened by an external force that exceeds their current force producing capacity. These unaccustomed eccentric activities often lead to muscle weakness, soreness, and inflammation. During aging, the ability to produce force under these conditions is reduced and appears to be due to not only reductions in muscle mass but also to alterations in the basic mechanisms of contraction. These alterations include impairments in the excitation-contraction process, and the action of the cross-bridges. Also, it is well known that age-related skeletal muscle atrophy is characterized by a preferential atrophy of fast fibers, and increased susceptibility to fast muscle fiber when aged muscles are exposed to eccentric contraction followed by the impaired recovery process has been reported. Taken together, the selective loss of fast muscle fiber in aged muscle could be affected by eccentric-induced muscle damage, which has significant implication to identify the etiology of the age-related functional changes. Therefore, in this review the alteration of age-related muscle function and its impact to/of eccentric induced muscle damage and recovery will be addressed in detail.

  6. Age-related decrease in physical activity and functional fitness among elderly men and women.

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    Milanović, Zoran; Pantelić, Saša; Trajković, Nebojša; Sporiš, Goran; Kostić, Radmila; James, Nic

    2013-01-01

    To determine differences in physical activity level and functional fitness between young elderly (60-69 years) and old elderly (70-80 years) people with the hypothesis that an age-related decline would be found. A total of 1288 participants' level of physical activity was evaluated using the International Physical Activity Questionnaire: 594 were male (mean ± standard deviation: body height 175.62 ± 9.78 cm; body weight 82.26 ± 31.33 kg) and 694 female (mean ± standard deviation: body height 165.17 ± 23.12 cm; body weight 69.74 ± 12.44 kg). Functional fitness was also estimated using the Senior Fitness Test: back scratch, chair sit and reach, 8-foot up and go, chair stand up for 30 seconds, arm curl, and 2-minute step test. Significant differences (P aging, among men and women older than 60 years, the value of the Metabolic Equivalent of Task in total physical activity significantly reduces (P aging process. These differences between young and old elderly people were due to the reduction of muscle strength in both upper and lower limbs and changes in body-fat percentage, flexibility, agility, and endurance.

  7. Rhythmic Spontaneous Activity Mediates the Age-Related Decline in Somatosensory Function.

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    Spooner, Rachel K; Wiesman, Alex I; Proskovec, Amy L; Heinrichs-Graham, Elizabeth; Wilson, Tony W

    2018-01-12

    Sensory gating is a neurophysiological process whereby the response to a second stimulus in a pair of identical stimuli is attenuated, and it is thought to reflect the capacity of the CNS to preserve neural resources for behaviorally relevant stimuli. Such gating is observed across multiple sensory modalities and is modulated by age, but the mechanisms involved are not understood. In this study, we examined somatosensory gating in 68 healthy adults using magnetoencephalography (MEG) and advanced oscillatory and time-domain analysis methods. MEG data underwent source reconstruction and peak voxel time series data were extracted to evaluate the dynamics of somatosensory gating, and the impact of spontaneous neural activity immediately preceding the stimulation. We found that gating declined with increasing age and that older adults had significantly reduced gating relative to younger adults, suggesting impaired local inhibitory function. Most importantly, older adults had significantly elevated spontaneous activity preceding the stimulation, and this effect fully mediated the impact of aging on sensory gating. In conclusion, gating in the somatosensory system declines with advancing age and this effect is directly tied to increased spontaneous neural activity in the primary somatosensory cortices, which is likely secondary to age-related declines in local GABA inhibitory function. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Endophenotypes for Age-Related Macular Degeneration: Extending Our Reach into the Preclinical Stages of Disease.

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    Gorin, Michael B; Weeks, Daniel E; Baron, Robert V; Conley, Yvette P; Ortube, Maria C; Nusinowitz, Steven

    2014-11-28

    The key to reducing the individual and societal burden of age-related macular degeneration (AMD)-related vision loss, is to be able to initiate therapies that slow or halt the progression at a point that will yield the maximum benefit while minimizing personal risk and cost. There is a critical need to find clinical markers that, when combined with the specificity of genetic testing, will identify individuals at the earliest stages of AMD who would benefit from preventive therapies. These clinical markers are endophenotypes for AMD, present in those who are likely to develop AMD, as well as in those who have clinical evidence of AMD. Clinical characteristics associated with AMD may also be possible endophenotypes if they can be detected before or at the earliest stages of the condition, but we and others have shown that this may not always be valid. Several studies have suggested that dynamic changes in rhodopsin regeneration (dark adaptation kinetics and/or critical flicker fusion frequencies) may be more subtle indicators of AMD-associated early retinal dysfunction. One can test for the relevance of these measures using genetic risk profiles based on known genetic risk variants. These functional measures may improve the sensitivity and specificity of predictive models for AMD and may also serve to delineate clinical subtypes of AMD that may differ with respect to prognosis and treatment.

  9. Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis.

    Science.gov (United States)

    Bianchi, Enrica; Scarinci, Fabio; Ripandelli, Guido; Feher, Janos; Pacella, Elena; Magliulo, Giuseppe; Gabrieli, Corrado Balacco; Plateroti, Rocco; Plateroti, Pasquale; Mignini, Fiorenzo; Artico, Marco

    2013-01-01

    Age-related macular degeneration (AMD) is the leading cause of impaired vision and blindness in the aging population. The aims of our studies were to identify qualitative and quantitative alterations in mitochondria in human retinal pigment epithelium (RPE) from AMD patients and controls and to test the protective effects of pigment epithelium-derived factor (PEDF), a known neurotrophic and antiangiogenic substance, against neurotrophic keratouveitis. Histopathological alterations were studied by means of morphometry, light and electron microscopy. Unexpectedly, morphometric data showed that the RPE alterations noted in AMD may also develop in normal aging, 10-15 years later than appearing in AMD patients. Reduced tear secretion, corneal ulceration and leukocytic infiltration were found in capsaicin (CAP)-treated rats, but this effect was significantly attenuated by PEDF. These findings suggest that PEDF accelerated the recovery of tear secretion and also prevented neurotrophic keratouveitis and vitreoretinal inflammation. PEDF may have a clinical application in inflammatory and neovascular diseases of the eye.

  10. Age-related changes in the cellular composition and epithelial organization of the mouse trachea.

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    Carolien Wansleeben

    Full Text Available We report here senescent changes in the structure and organization of the mucociliary pseudostratified epithelium of the mouse trachea and main stem bronchi. We confirm previous reports of the gradual appearance of age-related, gland-like structures (ARGLS in the submucosa, especially in the intercartilage regions and carina. Immunohistochemistry shows these structures contain ciliated and secretory cells and Krt5+ basal cells, but not the myoepithelial cells or ciliated ducts typical of normal submucosal glands. Data suggest they arise de novo by budding from the surface epithelium rather than by delayed growth of rudimentary or cryptic submucosal glands. In old mice the surface epithelium contains fewer cells per unit length than in young mice and the proportion of Krt5+, p63+ basal cells is reduced in both males and females. However, there appears to be no significant difference in the ability of basal stem cells isolated from individual young and old mice to form clonal tracheospheres in culture or in the ability of the epithelium to repair after damage by inhaled sulfur dioxide. Gene expression analysis by Affymetrix microarray and quantitative PCR, as well as immunohistochemistry and flow sorting studies, are consistent with low-grade chronic inflammation in the tracheas of old versus young mice and an increase in the number of immune cells. The significance of these changes for ARGL formation are not clear since several treatments that induce acute inflammation in young mice did not result in budding of the surface epithelium.

  11. The determination of genetic markers of age-related cancer pathologies in populations from Kazakhstan

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    Leyla Bulatovna Djansugurova

    2013-05-01

    Full Text Available Aging associates with a variety of pathological conditions such as cancer, cardiovascular, neurodegenerative, autoimmune diseases, and metabolic disorders. The oncogenic alterations overlap frequently with the genes linked to aging. Here, we show that several aging related genes may serve as the genetic risk factors for cervical and esophagus cancers. In our study, we analyzed samples obtained from 115 patients with esophageal and 207 patients with cervical cancer. The control groups were selected to match the ethnicity and age of cancer patients. We examined the genes involved in the processes of xenobiotics detoxification (GSTM1 and GSTT1, DNA repair (XRCC1 and XRCC3, and cell cycle regulation and apoptosis (CCND1 and TP53. Our study revealed that deletions of GSTT1 and GSTM1 genes or the distinct point mutations of XRCC1 gene are associated with cervical and esophageal cancers. These results will lead to development of screening for detection of individuals susceptible to esophageal and cervical cancers. Introduction of the screening programs will allow the early and effective preventive measures that will reduce cancer incidence and mortality in Kazakhstan.

  12. Visual function and performance with blue-light blocking filters in age-related macular degeneration.

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    Kiser, Ava K; Deschler, Emily K; Dagnelie, Gislin

    2008-08-01

    Some dispute has occurred over the use of blue-light-attenuating intraocular lenses in age-related macular degeneration (AMD), as they may reduce scotopic vision. This study aimed to determine if a blue blocking filter would affect performance during eye-hand coordination and mobility tasks in scotopic illumination, psychophysically measured scotopic sensitivity or colour discrimination in AMD patients. Scotopic measures performed with and without a blue-attenuating filter included a mobility obstacle course, manipulation of cylindrical blocks and a psychophysical dark-adapted full-field flash test. A navy and blue sock colour sorting task evaluated photopic colour discrimination. Subjects were 22 bilateral pseudophakes with early AMD and visual acuity >6/24. On average with the filter, there was a 13% increase in time during the block test. The differences in time and number of bumps with versus without the filter were not significant for the mobility course. Performance with and without the filter was well correlated for the blocks (r = 0.70), flash test (r = 0.83) and mobility (r = 0.66), and the regression slopes were not significantly different from unity. 77% of subjects misidentified at least one navy sock as black with the filter compared with 9% without, with a significant increase in such misidentifications with the filter. The difference in scotopic visual function or performance with versus without a blue-blocking filter most likely does not produce a clinically significant effect or risk; however, detection of navy colour may be impaired.

  13. Age-related differences in orienting attention to sound object representations.

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    Alain, Claude; Cusimano, Madeline; Garami, Linda; Backer, Kristina C; Habelt, Bettina; Chan, Vanessa; Hasher, Lynn

    2018-02-09

    We examined the effect of age on listeners' ability to orient attention to an item in auditory short-term memory (ASTM) using high-density electroencephalography, while participants completed a delayed match-to-sample task. During the retention interval, an uninformative or an informative visual retro-cue guided attention to an item in ASTM. Informative cues speeded response times, but only for young adults. In young adults, informative retro-cues generated greater event-related potential amplitude between 450 and 650 ms at parietal sites, and an increased sustained potential over the left central scalp region, thought to index the deployment of attention and maintenance of the cued item in ASTM, respectively. Both modulations were reduced in older adults. Alpha and low beta oscillatory power suppression was greater when the retro-cue was informative than uninformative, especially in young adults. Our results point toward an age-related decline in orienting attention to the cued item in ASTM. Older adults may be dividing their attention between all items in working memory rather than selectively focusing attention on a single cued item. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Evolving Knowledge in Pharmacologic Treatments of Age-Related Macular Degeneration.

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    Soubrane Daguet, Gisèle; Risard-Gasiorowski, Sarah; Massamba, Nathalie

    2016-01-01

    Modern retinal drug therapy is a result of the recent challenges and breakthroughs in chemistry, physics, genetics, cell biology and biotechnologies. Specific pharmaceutical and pharmacokinetic characteristics of a drug are of major importance and contribute to its ability to penetrate targeted ocular tissues in order to result in effective therapeutic concentrations. In addition, the drugs should maintain a prolonged time of activity and be safe with minimal local and systemic toxicity. The transporter vehicle or drug delivery system is crucial in order to enhance ocular tissue penetration and establish controlled drug release. Administration methods should be local, thereby reducing systemic side effects, and, ideally, treatment should be noninvasive. Within the group of so-called classic therapies, the use of pharmacologic treatments has become widespread for most severe retinal diseases. Thereby, ocular therapy of diseases like exudative age-related macular degeneration has improved markedly. Moreover, new metabolic pathways have been identified, new molecules have emerged, new synthesis technologies have been discovered, and new formulae conceived. These developments have opened new avenues for limiting disease progression. © 2016 S. Karger AG, Basel.

  15. Submacular hemorrhage in neovascular age-related macular degeneration: A synthesis of the literature.

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    Stanescu-Segall, Dinu; Balta, Florian; Jackson, Timothy L

    2016-01-01

    Large submacular hemorrhage, an uncommon manifestation of neovascular age-related macular degeneration, may also occur with idiopathic polypoidal choroidal vasculopathy. Submacular hemorrhage damages photoreceptors owing to iron toxicity, fibrin meshwork contraction, and reduced nutrient flux, with subsequent macular scarring. Clinical and experimental studies support prompt treatment, as tissue damage can occur within 24 hours. Without treatment the natural history is poor, with a mean final visual acuity (VA) of 20/1600. Reported treatments include retinal pigment epithelial patch, macular translocation, pneumatic displacement, intravitreal or subretinal tissue plasminogen activator, intravitreal anti-vascular endothelial growth factor (VEGF) drugs, and combinations thereof. In the absence of comparative studies, we combined eligible studies to assess the VA change before and after each treatment option. The greatest improvement occurred after combined pars plana vitrectomy, subretinal tissue plasminogen activator, intravitreal gas, and anti-vascular endothelial growth factor treatment, with VA improving from 20/1000 to 20/400. The best final VA occurred using combined intravitreal tissue plasminogen activator, gas, and anti-vascular endothelial growth factor therapy, with VA improving from 20/200 to 20/100. Both treatments had an acceptable safety profile, but most studies were small, and larger randomized controlled trials are needed to determine both safety and efficacy. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  16. Induced pluripotent stem cell-based therapy for age-related macular degeneration.

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    Bracha, Peter; Moore, Nicholas A; Ciulla, Thomas A

    2017-09-01

    In age-related macular degeneration (AMD), stem cells could possibly replace or regenerate disrupted pathologic retinal pigment epithelium (RPE), and produce supportive growth factors and cytokines such as brain-derived neurotrophic factor.  Induced pluripotent stem cells (iPSCs)-derived RPE was first subretinally transplanted in a neovascular AMD patient in 2014. Areas covered: Induced PSCs are derived from the introduction of transcription factors to adult cells under specific cell culture conditions, followed by differentiation into RPE cells. Induced PSC-derived RPE cells exhibit ion transport, membrane potential, polarized VEGF secretion and gene expression that is similar to native RPE. Despite having similar in vitro function, morphology, immunostaining and microscopic analysis, it remains to be seen if iPSC-derived RPE can replicate the myriad of in vivo functions, including immunomodulatory effects, of native RPE cells.  Historically, adjuvant RPE transplantation during CNV resections were technically difficult and complicated by immune rejection. Autologous iPSCs are hypothesized to reduce the risk of immune rejection, but their production is time-consuming and expensive.  Alternatively, allogenic transplantation using human leukocyte antigen (HLA)-matched iPSCs, similar to HLA-matched organ transplantation, is currently being investigated. Expert opinion: Challenges to successful transplantation with iPSCs include surgical technique, a pathologic subretinal microenvironment, possible immune rejection, and complications of immunosuppression.

  17. Age-related differences in EEG beta activity during an assessment of ankle proprioception.

    Science.gov (United States)

    Toledo, Diana R; Barela, José A; Manzano, Gilberto M; Kohn, André F

    2016-05-27

    The aim of this work was to compare cortical beta oscillatory activity between young (YA) and older (OA) adults during the assessment of ankle proprioception. We analyzed the response time (RT) to kinesthetic perception and beta event-related desynchronization/synchronization (ERD/ERS) in response to passive ankle movement applied at a slow speed, 0.5°/s. The relationship between ERD/ERS and RT was investigated by classifying the signals into fast-, medium-, and slow-RT. The results showed a temporal relationship between beta oscillation changes and RT for both groups, i.e., earlier ERD and ERS were obtained for trials with faster response time. ERD was larger and delayed in OA compared to the YA, and beta ERS was present only for OA. These findings suggest that a less efficient proprioceptive signaling reaching the brain of OA requires a higher level of brain processing and hence the differences in ERD potentials between YA and OA. Furthermore, the occurrence of ERS in OA might represent a compensatory strategy of active cortical resetting for adequate sensorimotor behavior due to the age-related reduced peripheral input and neuromuscular impairments. Altered balance between excitatory and inhibitory intracortical activity in older adults presumably explains the changes in beta oscillations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury.

    Science.gov (United States)

    Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Ban, Tae Hyun; Jang, In-Ae; Yoon, Hye Eun; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2018-01-11

    Two important issues in the aging kidney are mitochondrial dysfunction and oxidative stress. An Nrf2 activator, resveratrol, is known to have various effects. Resveratrol may prevent inflammation and oxidative stress by activating Nrf2 and SIRT1 signaling. We examined whether resveratrol could potentially ameliorate the cellular condition, such as renal injury due to cellular oxidative stress and mitochondrial dysfunction caused by aging. Male 18-month-old C57BL/6 mice were used. Resveratrol (40 mg/kg) was administered to aged mice for 6 months. We compared histological changes, oxidative stress, and aging-related protein expression in the kidney between the resveratrol-treated group (RSV) and the control group (cont). We performed experiments using small-interfering RNAs (siRNAs) for Nrf2 and SIRT1 in cultured HK2 cells. Resveratrol improved renal function, proteinuria, histological changes and inflammation in aging mice. Also, expression of Nrf2-HO-1-NOQ-1 signaling and SIRT1-AMPK-PGC-1α signaling was increased in the RSV group. Transfection with Nrf2 and SIRT1 siRNA prevented resveratrol-induced anti-oxidative effect in HK2 cells in media treated with H 2 O 2 . Activation of the Nrf2 and SIRT1 signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Pharmacological targeting of Nrf2 signaling molecules may reduce the pathologic changes of aging in the kidney.

  19. Age-related changes in normal adult pancreas: MR imaging evaluation

    International Nuclear Information System (INIS)

    Sato, Tomohiro; Ito, Katsuyoshi; Tamada, Tsutomu; Sone, Teruki; Noda, Yasufumi; Higaki, Atsushi; Kanki, Akihiko; Tanimoto, Daigo; Higashi, Hiroki

    2012-01-01

    Objective: To investigate age-related changes in normal adult pancreas as identified by magnetic resonance imaging (MRI). Materials and methods: We examined 115 patients without pancreatic diseases (21–90 years) who underwent upper abdominal MRI to evaluate the normal pancreatic MRI findings related to aging. The parameters examined were the pancreatic anteroposterior (AP) diameter, pancreatic lobulation, pancreatic signal intensity (SI), depiction of the main pancreatic duct (MPD), grade of the visual SI decrease on the opposed-phase T1-weighted images compared with in-phase images, and enhancement effect of the pancreas in the arterial phase of dynamic imaging. Results: The pancreatic AP diameter significantly reduced (head, p = 0.0172; body, p = 0.0007; tail, p < 0.0001), and lobulation (p < 0.0001) and parenchymal fatty change (p < 0.0001) became more evident with aging. No significant correlation was observed between aging and pancreatic SI, however the SI on the in-phase T1-weighted images tended to decrease with aging. No significant correlation was observed between aging and the depiction of the MPD as well as aging and contrast enhancement. Conclusion: MRI findings of pancreatic atrophy, lobulation, and fatty degeneration are characteristic changes related to aging, and it is necessary to recognize these changes in the interpretation of abdominal MRI in patients with and without pancreatic disease

  20. Endophenotypes for Age-Related Macular Degeneration: Extending Our Reach into the Preclinical Stages of Disease

    Directory of Open Access Journals (Sweden)

    Michael B. Gorin

    2014-11-01

    Full Text Available The key to reducing the individual and societal burden of age-related macular degeneration (AMD-related vision loss, is to be able to initiate therapies that slow or halt the progression at a point that will yield the maximum benefit while minimizing personal risk and cost. There is a critical need to find clinical markers that, when combined with the specificity of genetic testing, will identify individuals at the earliest stages of AMD who would benefit from preventive therapies. These clinical markers are endophenotypes for AMD, present in those who are likely to develop AMD, as well as in those who have clinical evidence of AMD. Clinical characteristics associated with AMD may also be possible endophenotypes if they can be detected before or at the earliest stages of the condition, but we and others have shown that this may not always be valid. Several studies have suggested that dynamic changes in rhodopsin regeneration (dark adaptation kinetics and/or critical flicker fusion frequencies may be more subtle indicators of AMD-associated early retinal dysfunction. One can test for the relevance of these measures using genetic risk profiles based on known genetic risk variants. These functional measures may improve the sensitivity and specificity of predictive models for AMD and may also serve to delineate clinical subtypes of AMD that may differ with respect to prognosis and treatment.

  1. The association between statin use and risk of age-related macular degeneration

    Science.gov (United States)

    Ma, Le; Wang, Yafeng; Du, Junhui; Wang, Mingxu; Zhang, Rui; Fu, Yihao

    2015-01-01

    The aim of the present study was to evaluate the association between statin use and the risk of age-related macular degeneration (AMD). A systematic search of the PubMed, EMBASE and ISI web of science databases was used to identify eligible published literatures without language restrictions up to April 2015. Summary relative ratios (RRs) and 95% CIs were estimated using a fixed-effect or random-effects model. A total of 14 studies met the inclusion criteria and were included in this meta-analysis. No significant association was observed between statin use and the risk of any AMD (RR, 0.95; 95% CI, 0.74–1.15); and stratified analysis showed that statins had a significantly different effects on early and late stages of AMD. For early AMD, statin use significantly reduced the risk approximately 17% (RR, 0.83; 95% CI, 0.66–0.99). At the late stage, we observed a significant protective association of statin use with exudative AMD (RR, 0.90; 95% CI, 0.80–0.99), in contrast with the absent association between statins and geographic atrophy (RR, 1.16; 95% CI, 0.77–1.56). These results demonstrated that statin use was protective for early and exudative AMD. Additional large prospective cohort studies and RCTs are required to determine the potential effect of statins on AMD prevention. PMID:26658620

  2. Age-related impairments in active learning and strategic visual exploration.

    Science.gov (United States)

    Brandstatt, Kelly L; Voss, Joel L

    2014-01-01

    Old age could impair memory by disrupting learning strategies used by younger individuals. We tested this possibility by manipulating the ability to use visual-exploration strategies during learning. Subjects controlled visual exploration during active learning, thus permitting the use of strategies, whereas strategies were limited during passive learning via predetermined exploration patterns. Performance on tests of object recognition and object-location recall was matched for younger and older subjects for objects studied passively, when learning strategies were restricted. Active learning improved object recognition similarly for younger and older subjects. However, active learning improved object-location recall for younger subjects, but not older subjects. Exploration patterns were used to identify a learning strategy involving repeat viewing. Older subjects used this strategy less frequently and it provided less memory benefit compared to younger subjects. In previous experiments, we linked hippocampal-prefrontal co-activation to improvements in object-location recall from active learning and to the exploration strategy. Collectively, these findings suggest that age-related memory problems result partly from impaired strategies during learning, potentially due to reduced hippocampal-prefrontal co-engagement.

  3. Prevalence of and risk factors for age-related macular degeneration in a multiethnic Asian cohort.

    Science.gov (United States)

    Cheung, Chui Ming Gemmy; Tai, E Shyong; Kawasaki, Ryo; Tay, Wan Ting; Lee, Jeannette L; Hamzah, Haslina; Wong, Tien Y

    2012-04-01

    To describe the prevalence of and risk factors for age-related macular degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian persons. In this population-based study, 3172 persons of Chinese, Malay, and Indian ethnicities 40 years and older were included. Participants underwent comprehensive systemic and ocular examination, retinal photography, and laboratory investigations. Early and late AMD signs were graded from retinal photographs. Age-standardized prevalence estimates were calculated using the 2010 Singapore adult population as the standard population. Association with a range of systemic risk factors was analyzed. Of 3172 participants, AMD was present in 211 subjects. Age-standardized prevalence of AMD was 7.0% in persons 40 years and older. The age-standardized prevalence was similar in all 3 Asian ethnic groups: Chinese, 7.3%; Malay, 7.7%; and Indian, 5.7% (P value = .44). The prevalence increased with age and was higher in men. Of the range of risk factors evaluated, only myopic refractive error (Chinese men. The prevalence of AMD was similar in the 3 major ethnic groups in Asia and comparable with white populations. Myopic refractive error was associated with reduced risk of AMD in Chinese men.

  4. Familiarization may minimize age-related declines in rule-based category learning.

    Science.gov (United States)

    Rabi, Rahel; Minda, John Paul

    2017-11-01

    Being able to categorize promotes cognitive economy by reducing the amount of information that an individual needs to remember. This ability is particularly important in older adulthood, when executive functioning abilities are known to decline. Prior research has shown that older adults can learn simple categories quite well but struggle when learning more complex categories which place a demand on executive function resources. The goal of Experiments 1 to 3 was to assess whether familiarizing older adults with complex rule-based or non-rule-based categories prior to beginning a categorization task would minimize age-related categorization deficits. Both rule-based and non-rule-based category learning improved among older adults following pretraining, but the improvements to rule-based learning were more drastic, suggesting that executive functioning plays a heavier role in rule-based category learning. Findings provide a potential solution for improving the category learning abilities of older adults. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  5. Age-Related Changes in the Ability to Switch between Temporal and Spatial Attention.

    Science.gov (United States)

    Callaghan, Eleanor; Holland, Carol; Kessler, Klaus

    2017-01-01

    Background : Identifying age-related changes in cognition that contribute towards reduced driving performance is important for the development of interventions to improve older adults' driving and prolong the time that they can continue to drive. While driving, one is often required to switch from attending to events changing in time, to distribute attention spatially. Although there is extensive research into both spatial attention and temporal attention and how these change with age, the literature on switching between these modalities of attention is limited within any age group. Methods : Age groups (21-30, 40-49, 50-59, 60-69 and 70+ years) were compared on their ability to switch between detecting a target in a rapid serial visual presentation (RSVP) stream and detecting a target in a visual search display. To manipulate the cost of switching, the target in the RSVP stream was either the first item in the stream (Target 1st), towards the end of the stream (Target Mid), or absent from the stream (Distractor Only). Visual search response times and accuracy were recorded. Target 1st trials behaved as no-switch trials, as attending to the remaining stream was not necessary. Target Mid and Distractor Only trials behaved as switch trials, as attending to the stream to the end was required. Results : Visual search response times (RTs) were longer on "Target Mid" and "Distractor Only" trials in comparison to "Target 1st" trials, reflecting switch-costs. Larger switch-costs were found in both the 40-49 and 60-69 years group in comparison to the 21-30 years group when switching from the Target Mid condition. Discussion : Findings warrant further exploration as to whether there are age-related changes in the ability to switch between these modalities of attention while driving. If older adults display poor performance when switching between temporal and spatial attention while driving, then the development of an intervention to preserve and improve this ability would be

  6. Neurogenetics of female reproductive behaviors in Drosophila melanogaster.

    Science.gov (United States)

    Laturney, Meghan; Billeter, Jean-Christophe

    2014-01-01

    We follow an adult Drosophila melanogaster female through the major reproductive decisions she makes during her lifetime, including habitat selection, precopulatory mate choice, postcopulatory physiological changes, polyandry, and egg-laying site selection. In the process, we review the molecular and neuronal mechanisms allowing females to integrate signals from both environmental and social sources to produce those behavioral outputs. We pay attention to how an understanding of D. melanogaster female reproductive behaviors contributes to a wider understanding of evolutionary processes such as pre- and postcopulatory sexual selection as well as sexual conflict. Within each section, we attempt to connect the theories that pertain to the evolution of female reproductive behaviors with the molecular and neurobiological data that support these theories. We draw attention to the fact that the evolutionary and mechanistic basis of female reproductive behaviors, even in a species as extensively studied as D. melanogaster, remains poorly understood. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Age-related changes in late I-waves influence motor cortex plasticity induction in older adults.

    Science.gov (United States)

    Opie, George M; Cirillo, John; Semmler, John G

    2018-04-18

    The response to neuroplasticity interventions using transcranial magnetic stimulation (TMS) is reduced in older adults, which may be due, in part, to age-related alterations in interneuronal (I-wave) circuitry. The current study investigated age-related changes in interneuronal characteristics and whether they influence motor cortical plasticity in older adults. While I-wave recruitment was unaffected by age, there was a shift in the temporal characteristics of the late, but not early I-waves. Using I-wave periodicity repetitive TMS (iTMS), we showed that these differences in I-wave characteristics influence the induction of cortical plasticity in older adults. Previous research shows that neuroplasticity assessed using transcranial magnetic stimulation (TMS) is reduced in older adults. While this deficit is often assumed to represent altered synaptic modification processes, age-related changes in the interneuronal circuits activated by TMS may also contribute. Here we assessed age-related differences in the characteristics of the corticospinal indirect (I) waves and how they influence plasticity induction in primary motor cortex. Twenty young (23.7 ± 3.4 years) and 19 older adults (70.6 ± 6.0 years) participated in these studies. I-wave recruitment was assessed by changing the direction of the current used to activate the motor cortex, whereas short-interval intracortical facilitation (SICF) was recorded to assess facilitatory I-wave interactions. In a separate study, I-wave periodicity TMS (iTMS) was used to examine the effect of I-wave latency on motor cortex plasticity. Data from the motor evoked potential (MEP) onset latency produced using different coil orientations suggested that there were no age-related differences in preferential I-wave recruitment (P = 0.6). However, older adults demonstrated significant reductions in MEP facilitation at all 3 SICF peaks (all P-values < 0.05) and a delayed latency of the second and third SICF peaks (all P

  8. Validation of anti-aging drugs by treating age-related diseases.

    Science.gov (United States)

    Blagosklonny, Mikhail V

    2009-03-28

    Humans die from age-related diseases, which are deadly manifestations of the aging process. In order to extend life span, an anti-aging drug must delay age-related diseases. All together age-related diseases are the best biomarker of aging. Once a drug is used for treatment of any one chronic disease, its effect against other diseases (atherosclerosis, cancer, prostate enlargement, osteoporosis, insulin resistance, Alzheimer's and Parkinson's diseases, age-related macular degeneration) may be evaluated in the same group of patients. If the group is large, then the anti-aging effect could be validated in a couple of years. Startlingly, retrospective analysis of clinical and preclinical data reveals four potential anti-aging modalities.

  9. Age-related differences in neurotoxicity produced by organophosphorus and N-methyl carbamate pesticides

    Science.gov (United States)

    Potential pesticide effects in infants and toddlers have received much attention in the scientific literature and the public media, including the concern for increased response to acute or shortterm exposures. Age-related differences in the acute neurotoxicity of acetylcholinest...

  10. Age-related functional limitations, countermeasures, and crash risks : traffic tech.

    Science.gov (United States)

    2012-03-01

    This study updates and extends our understanding of how : age-related functional deficits, including changes in vision, : cognition, strength, and flexibility can increase older drivers : crash risks. The report discusses the potential of a variet...

  11. Serum APOE, leptin, CFH and HTRA1 levels in Pakistani age related macular degeneration patients.

    Science.gov (United States)

    Qureshi, Irfan Zia; Ambreen, Fareeha

    2017-06-01

    To determine the association between serum levels of apolipoprotein E, leptin, complimentary factor H and high temperature requirement A-1 in patients with age-related macular degeneration. This case-control study was conducted at the Quaid-i-Azam University, Islamabad, Pakistan, from May to October 2013, and comprised patients with age-related macular degeneration and matching controls. The confirmation of age-related macular degeneration was carried out through slit lamp examination, fundoscopy and ocular coherence tomography. The selected subjects were not suffering with any other systemic or ophthalmic complication(s). Serum apolipoprotein E, leptin, complimentary factor H and high temperature requirement A-1 were estimated in serum samples of all subjects. SPSS 18 was used for data analysis. Of the 190 participants, 90(47.4%) were patients with age-related macular degeneration and 100(52.6%) were controls. Significantly elevated serum apolipoprotein E (page-related macular degeneration patients.

  12. Age-related changes in sleep EEG are attenuated in highly intelligent individuals.

    Science.gov (United States)

    Pótári, Adrián; Ujma, Péter P; Konrad, Boris N; Genzel, Lisa; Simor, Péter; Körmendi, János; Gombos, Ferenc; Steiger, Axel; Dresler, Martin; Bódizs, Róbert

    2017-02-01

    Impaired sleep is a frequent complaint in ageing and a risk factor for many diseases. Non-rapid eye movement (NREM) sleep EEG delta power reflects neural plasticity and, in line with age-related cognitive decline, decreases with age. Individuals with higher general intelligence are less affected by age-related cognitive decline or other disorders and have longer lifespans. We investigated the correlation between age and EEG power in 159 healthy human subjects (age range: 17-69 years), and compared an average (IQIQ≥120; N=72) intelligence subgroup. We found less age-related decrease in all-night relative NREM sleep EEG delta power in the high intelligence subgroup. Our results suggest that highly intelligent individuals are less affected by the sleep-related effects of biological ageing, and therefore potentially less at risk for age-related cognitive deficits and other diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Aging Changes in Retinal Microglia and their Relevance to Age-related Retinal Disease.

    Science.gov (United States)

    Ma, Wenxin; Wong, Wai T

    2016-01-01

    Age-related retinal diseases, such as age-related macular degeneration (AMD) and glaucoma, contain features of chronic retinal inflammation that may promote disease progression. However, the relationship between aging and neuroinflammation is unclear. Microglia are long-lived, resident immune cells of the retina, and mediate local neuroinflammatory reactions. We hypothesize that aging changes in microglia may be causally linked to neuroinflammatory changes underlying age-dependent retinal diseases. Here, we review the evidence for (1) how the retinal microglial phenotype changes with aging, (2) the factors that drive microglial aging in the retina, and (3) aging-related changes in microglial gene expression. We examine how these aspects of microglial aging changes may relate to pathogenic mechanisms of immune dysregulation driving the progression of age-related retinal disease. These relationships can highlight microglial aging as a novel target for the prevention and treatment of retinal disease.

  14. Irradiation-resistance conferred by superoxide dismutase: possible adaptive role of a natural polymorphism in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Peng, T.X.; Moya, A.; Ayala, F.J.

    1986-01-01

    The toxic effects of ionizing radiation to DNA are thought to be due to the generation of the superoxide radical, 02-. Superoxide dismutase (SOD), which scavenges 02-., has been invoked as a protecting enzyme against ionizing radiation in viruses, bacteria, mammalian cells in culture, and live mice. We now demonstrate that SOD is involved in the resistance of Drosophila melanogaster against irradiation. The protection is greatest when flies carry the S form of the enzyme (which exhibits highest in vitro specific activity), intermediate when they carry the F form of the enzyme, and lowest when they are homozygous for N, an allele that reduces the amount of the enzyme to 3.5% of the normal level. Natural selection experiments show that the fitness of the high-activity S allele is increased in an irradiated population relative to the nonirradiated control. These results point towards a possible adaptive function of the S/F polymorphism found in natural populations of D. melanogaster

  15. MRI of spinal bone marrow: part I, techniques and normal age-related appearances.

    Science.gov (United States)

    Shah, Lubdha M; Hanrahan, Christopher J

    2011-12-01

    This article reviews MRI protocols, including routine and nonroutine pulse sequences as well as the normal MRI appearance of spinal marrow and expected age-related changes. Routine MRI of the spine provides useful evaluation of the spinal bone marrow, but nonroutine MRI pulse sequences are increasingly being used to evaluate bone marrow pathology. An understanding of MRI pulse sequences and the normal and age-related appearances of bone marrow is important for the practicing radiologist.

  16. Public opinion on age-related degradation in nuclear power plants

    International Nuclear Information System (INIS)

    Matsuda, Toshihiro

    2005-01-01

    The first objective of this study is to shed light on the public opinion on age-related degradation at nuclear power plants, namely, on how the general public recognizes or views age-related degradation, which is a safety-related issue and one of the factors contributing to accidents and failures which occur at nuclear power plants. The second objective is to look into the impacts of the accident at Mihama Unit 3, which was caused by a failure to check on the piping wall thickness, on the public opinion on age-related degradation. The first survey was conducted in August 2003, followed by the second survey in October 2004, two months after the accident. The surveys found that the age-related degradation is being perceived by people as one of the risk factors that affect the safety of nuclear power plants. The characteristics of the citizens' perceptions toward age-related degradation in the form of piping cracks are that: (a) many respondents feel uneasy but a relatively few people consider that nuclear operators are technologically capable of coping with this problem; (b) many people believe that radioactivity may be released; and (c) numerous respondents consider that signs of cracks must be thoroughly detected through inspections, while on the other hand, a large percentage of the respondents attribute the accident to improper inspections/maintenance. Based on these results, the government and nuclear operators are expected to give most illuminating explanation on the current situation of and remedial measures against age-related degradation at nuclear power plants. As for the effects of the Mihama-3 accident on the public opinion on age-related degradation, it was revealed that the accident has not so significantly affected the general view for the safety of nuclear power plants, but has newly or strongly aroused people's consciousness of two of the risk factors - improper inspections/maintenance and the age-related degradation of piping. (author)

  17. Motor Control and Aging: Links to Age-Related Brain Structural, Functional, and Biochemical Effects

    OpenAIRE

    Seidler, Rachael D.; Bernard, Jessica A.; Burutolu, Taritonye B.; Fling, Brett W.; Gordon, Mark T.; Gwin, Joseph T.; Kwak, Youngbin; Lipps, David B.

    2009-01-01

    Although connections between cognitive deficits and age-associated brain differences have been elucidated, relationships with motor performance are less well understood. Here, we broadly review age-related brain differences and motor deficits in older adults in addition to cognition-action theories. Age-related atrophy of the motor cortical regions and corpus callosum may precipitate or coincide with motor declines such as balance and gait deficits, coordination deficits, and movement slowing...

  18. Self-reported optometric practise patterns in age-related macular degeneration.

    Science.gov (United States)

    Ly, Angelica; Nivison-Smith, Lisa; Zangerl, Barbara; Assaad, Nagi; Kalloniatis, Michael

    2017-11-01

    The use of advanced imaging in clinical practice is emerging and the use of this technology by optometrists in assessing patients with age-related macular degeneration is of interest. Therefore, this study explored contemporary, self-reported patterns of practice regarding age-related macular degeneration diagnosis and management using a cross-sectional survey of optometrists in Australia and New Zealand. Practising optometrists were surveyed on four key areas, namely, demographics, clinical skills and experience, assessment and management of age-related macular degeneration. Questions pertaining to self-rated competency, knowledge and attitudes used a five-point Likert scale. Completed responses were received from 127 and 87 practising optometrists in Australia and New Zealand, respectively. Advanced imaging showed greater variation in service delivery than traditional techniques (such as slitlamp funduscopy) and trended toward optical coherence tomography, which was routinely performed in age-related macular degeneration by 49 per cent of respondents. Optical coherence tomography was also associated with higher self-rated competency, knowledge and perceived relevance to practice than other modalities. Most respondents (93 per cent) indicated that they regularly applied patient symptoms, case history, visual function results and signs from traditional testing, when queried about their management of patients with age-related macular degeneration. Over half (63 per cent) also considered advanced imaging, while 31 per cent additionally considered all of these as well as the disease stage and clinical guidelines. Contrary to the evidence base, 68 and 34 per cent rated nutritional supplements as highly relevant or relevant in early age-related macular degeneration and normal aging changes, respectively. These results highlight the emergence of multimodal and advanced imaging (especially optical coherence tomography) in the assessment of age-related macular degeneration

  19. Incidence of legal blindness from age-related macular degeneration in denmark: year 2000 to 2010

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi; Larsen, Michael; Munch, Inger Christine

    2012-01-01

    To report incidence rates of legal blindness from age-related macular degeneration (AMD) and other causes in Denmark from years 2000 to 2010 in the age group at risk of AMD aged 50 years and older.......To report incidence rates of legal blindness from age-related macular degeneration (AMD) and other causes in Denmark from years 2000 to 2010 in the age group at risk of AMD aged 50 years and older....

  20. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

    Science.gov (United States)

    Rastogi, Neelesh; Smith, R Theodore

    2016-01-01

    Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Association of HTRA1 rs11200638 with age-related macular degeneration (AMD) in Brazilian patients.

    Science.gov (United States)

    Lana, Tamires Prates; da Silva Costa, Sueli Matilde; Ananina, Galina; Hirata, Fábio Endo; Rim, Priscila Hae Hyun; Medina, Flávio MacCord; de Vasconcellos, José Paulo Cabral; de Melo, Mônica Barbosa

    2018-01-01

    Age-related macular degeneration is a multifactorial disease that can lead to vision impairment in older individuals. Although the etiology of age-related macular degeneration remains unknown, risk factors include age, ethnicity, smoking, hypertension, obesity, and genetic factors. Two main loci have been identified through genome-wide association studies, on chromosomes 1 and 10. Among the variants located at the 10q26 region, rs11200638, located at the HTRA1 gene promoter, has been associated with age-related macular degeneration in several populations and is considered the main polymorphism. We conducted a replication case-control study to analyze the frequency and participation of rs11200638 in the etiology of age-related macular degeneration in a sample of patients and controls from the State of São Paulo, Brazil, through polymerase chain reaction and enzymatic digestion. The frequency of the A allele was 57.60% in patients with age-related macular degeneration and 36.45% in controls (p value macular degeneration group compared to the control group (p = 1.21 e-07 and 0.0357, respectively). No statistically significant results were observed after stratification in dry versus wet types or advanced versus non-advanced forms. To our knowledge, this is the first time the association between rs11200638 and overall age-related macular degeneration has been reported in South America.

  2. Age-related differences in brain activity in the subsequent memory paradigm: a meta-analysis.

    Science.gov (United States)

    Maillet, David; Rajah, M Natasha

    2014-09-01

    Healthy aging is associated with declines in episodic memory. This reduction is thought to be due in part to age-related differences in encoding-related processes. In the current study, we performed an activation likelihood estimation meta-analysis of functional magnetic resonance imaging (fMRI) studies assessing age-related differences in the neural correlates of episodic encoding. Only studies using the subsequent memory paradigm were included. We found age-related under-recruitment of occipital and fusiform cortex, but over-recruitment in a set of regions including bilateral middle/superior frontal gyri, anterior medial frontal gyrus, precuneus and left inferior parietal lobe. We demonstrate that all of the regions consistently over-recruited by older adults during successful encoding exhibit either direct overlap, or occur in close vicinity to regions consistently involved in unsuccessful encoding in young adults. We discuss the possibility that this overall pattern of age-related differences represents an age-related shift in focus: away from perceptual details, and toward evaluative and personal thoughts and feelings during memory tasks. We discuss whether these age-related differences in brain activation benefit performance in older adults, and additional considerations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Mutagenic effects of irradiated glucose in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Varma, M.B.; Rao, K.P.; Nandan, S.D.; Rao, M.S.

    1982-01-01

    The mutagenic effects of irradiated glucose were studied using the sex-linked recessive lethal test in Drosophila melanogaster. Oregon K males of D. melanogaster reared on a medium containing 20 or 40% glucose irradiated with a dose of 0.02, 0.10, 0.20, 2 or 5 Mrad #betta#-rays were scored for the induction of sex-linked recessive lethals. The results showed no significant increase in the frequency of X-lethals in Drosophila at any of the dose levels. (author)

  4. Developmental acclimation to low or high humidity conditions affect starvation and heat resistance of Drosophila melanogaster.

    Science.gov (United States)

    Parkash, Ravi; Ranga, Poonam; Aggarwal, Dau Dayal

    2014-09-01

    Several Drosophila species originating from tropical humid localities are more resistant to starvation and heat stress than populations from high latitudes but mechanistic bases of such physiological changes are largely unknown. In order to test whether humidity levels affect starvation and heat resistance, we investigated developmental acclimation effects of low to high humidity conditions on the storage and utilization of energy resources, body mass, starvation survival, heat knockdown and heat survival of D. melanogaster. Isofemale lines reared under higher humidity (85% RH) stored significantly higher level of lipids and showed greater starvation survival hours but smaller in body size. In contrast, lines reared at low humidity evidenced reduced levels of body lipids and starvation resistance. Starvation resistance and lipid storage level were higher in females than males. However, the rate of utilization of lipids under starvation stress was lower for lines reared under higher humidity. Adult flies of lines reared at 65% RH and acclimated under high or low humidity condition for 200 hours also showed changes in resistance to starvation and heat but such effects were significantly lower as compared with developmental acclimation. Isofemale lines reared under higher humidity showed greater heat knockdown time and heat-shock survival. These laboratory observations on developmental and adult acclimation effects of low versus high humidity conditions have helped in explaining seasonal changes in resistance to starvation and heat of the wild-caught flies of D. melanogaster. Thus, we may suggest that wet versus drier conditions significantly affect starvation and heat resistance of D. melanogaster. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. The Evaluation of Geroprotective Effects of Selected Flavonoids in Drosophila melanogaster and Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Ekaterina Lashmanova

    2017-12-01

    Full Text Available Flavonoids is an intensively studied group of natural compounds with antioxidant, antineoplastic, antihyperglycemic, cardioprotective, and neuroprotective properties. The present study intends to investigate the geroprotective action of three selected flavonoids (naringin, luteolin, chrysin in two model organisms, Caenorhabditis elegans and Drosophila melanogaster. Luteolin and chrysin were shown to improve lifespan parameters when administered to both model organisms. The observed positive effects of these flavonoids in D. melanogaster were limited to females and were not associated with reduced fecundity or locomotor impairment. The life-extending effects of flavonoids were observed in N2 wild-type worms but absent in aak-2(gt33 mutants implying that these effects can be associated with AMP-activated protein kinase activity. Naringin improved lifespan parameters of C. elegans, but had no effect on D. melanogaster females; in some cases, naringin was found to decrease the lifespan of males. Compared to chrysin and luteolin, however, naringin more effectively activates Nrf2 target genes (particularly, GstD1 under oxidative stress. Then we compared molecular mechanisms of studied compounds and a well-known geroprotector rapamycin, using software tool GeroScope. There are no transcriptomic data on luteolin or chrysin provided by LINCS Project database. The bioinformatics comparison of transcriptomics data for A549 and MCF7 human cell lines treated with rapamycin or naringin revealed that these compounds share just a few common signaling pathways and quite distinct in their geroprotective action. Thus, based on C. elegans effects of naringin, luteolin, chrysin on lifespan we have revealed new potential geroprotectors.

  6. Influence of Quercetin in the Temporal Regulation of Redox Homeostasis in Drosophila melanogaster.

    Science.gov (United States)

    Subramanian, Perumal; Kaliyamoorthy, Kanimozhi; Jayapalan, Jaime Jacqueline; Abdul-Rahman, Puteri Shafinaz; Haji Hashim, Onn

    2017-01-01

    Numerous biological processes are governed by the biological clock. Studies using Drosophila melanogaster (L.) are valuable that could be of importance for their effective applications on rodent studies. In this study, the beneficial role of quercetin (a flavonoid) on H2O2 induced stress in D. melanogaster was investigated. D. melanogaster flies were divided into four groups (group I - control, group II - H2O2 (acute exposure), group III - quercetin, and group IV - quercetin + H2O2 treated). Negative geotaxis assay, oxidative stress indicators (protein carbonyls, thiobarbituric reactive substances [TBARS]), and antioxidants (superoxide dismutase [SOD], catalase [CAT], glutathione-S-transferase [GST], glutathione peroxidase, and reduced glutathione [GSH]) were measured at 4 h intervals over 24 h and temporal expression of heat shock protein-70 (Hsp70), Upd1 (homolog of IL-6 in Drosophila), and nitric oxide synthase (Nos) was analyzed by Western blotting. Groups II and IV showed altered biochemical rhythms (compared with controls). Decreased mesor values of negative geotaxis, SOD, CAT, GST, and GSH were noticed in H2O2, increased mesor of oxidative stress indicators (TBARS and protein carbonyl content) and a reversibility of the rhythmic characteristics were conspicuous after quercetin treatment. The expression levels of Hsp70, Upd1, and Nos were noticeably maximum at 04:00. Significant elevation of expression by H2O2 was nearly normalized by quercetin treatment. The possible mechanism by which quercetin modulates oxidant-antioxidant imbalance under oxidative stress could be ascribed to the modulation of the rhythmic properties. Our results will be helpful to understand the molecular interlink between circadian rhythm and oxidative stress mechanism. © The Author 2017. Published by Oxford University Press on behalf of the Entomological Society of America.

  7. Arm-Gal4 inheritance influences development and lifespan in Drosophila melanogaster.

    Science.gov (United States)

    Slade, F A; Staveley, B E

    2015-10-19

    The UAS-Gal4 ectopic expression system is a widely used and highly valued tool that allows specific gene expression in Drosophila melanogaster. Yeast transcription factor Gal4 can be directed using D. melanogaster transcriptional control elements, and is often assumed to have little effect on the organism. By evaluation of the consequences of maternal and paternal inheritance of a Gal4 transgene under the transcriptional regulation of armadillo control elements (arm-Gal4), we demonstrated that Gal4 expression could be detrimental to development and longevity. Male progeny expressing arm-Gal4 in the presence of UAS-lacZ transgene had reduced numbers and size of ommatidia, compared to flies expressing UAS-lacZ transgene under the control of other Gal4 transgenes. Aged at 25°C, the median life span of male flies with maternally inherited elav-Gal4 was 70 days, without a responding transgene or with UAS-lacZ. The median life span of maternally inherited arm-Gal4 male flies without a responding transgene was 48 days, and 40 days with the UAS-lacZ transgene. A partial rescue of this phenotype was observed with the expression of UAS-lacZ under paternal arm-Gal4 control, having an average median lifespan of 60 days. This data suggests that arm-Gal4 has detrimental effects on Drosophila development and lifespan that are directly dependent upon parental inheritance, and that the benign responder and reporter gene UAS-lacZ may influence D. melanogaster development. These findings should be taken into consideration during the design and execution of UAS-Gal4 expression experiments.

  8. Expression and mechanism of mammalian target of rapamycin in age-related renal cell senescence and organ aging.

    Science.gov (United States)

    Zhuo, Li; Cai, Guangyan; Liu, Fuyou; Fu, Bo; Liu, Weiping; Hong, Quan; Ma, Qiang; Peng, Youming; Wang, Jianzhong; Chen, Xiangmei

    2009-10-01

    The mammalian target of rapamycin (mTOR) is relevant to cell senescence and organismal aging. This study firstly showed that the level of mTOR expression increased with aging in rat kidneys, rat mesangial cells and WI-38 cells (P aging-related phenotypes were all reduced in cells treated with rapamycin (an inhibitor of mTOR) than in control cells (P aging, and that mTOR may promote cellular senescence by regulating the cell cycle through p21(WAF1/CIP1/SDI1), which might provide a new target for preventing renal aging.

  9. Silencing D. melanogaster lgr1 impairs transition from larval to pupal stage.

    Science.gov (United States)

    Vandersmissen, Hans Peter; Van Hiel, Matthias Boris; Van Loy, Tom; Vleugels, Rut; Vanden Broeck, Jozef

    2014-12-01

    G protein-coupled receptors (GPCRs) play key roles in a wide diversity of physiological processes and signalling pathways. The leucine-rich repeats containing GPCRs (LGRs) are a subfamily that is well-conserved throughout most metazoan phyla and have important regulatory roles in vertebrates. Here, we report on the critical role of Drosophila melanogaster LGR1, the fruit fly homologue of the vertebrate glycoprotein hormone receptors, in development as a factor involved in the regulation of pupariation. Transcript profiling revealed that lgr1 transcripts are most abundant in third instar larvae and adult flies. The tissues displaying the highest transcript levels were the hindgut, the rectum and the salivary glands. Knockdown using RNA interference (RNAi) demonstrated that white pupa formation was severely suppressed in D. melanogaster lgr1 RNAi larvae. Associated with this developmental defect was a reduced ecdysteroid titer, which is in line with significantly reduced transcript levels detected for the Halloween genes shadow (sad) and spookier (spok) in the third instar lgr1 RNAi larvae compared to the control condition. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Concomitant changes in radiation resistance and trehalose levels during life stages of Drosophila melanogaster suggest radio-protective function of trehalose.

    Science.gov (United States)

    Paithankar, Jagdish Gopal; Raghu, Shamprasad Varija; Patil, Rajashekhar K

    2018-04-20

    During development, various life stages of Drosophila melanogaster (D. melanogaster) show different levels of resistance to gamma irradiation, with the early pupal stage being the most radiation sensitive. This provides us an opportunity to explore the biochemical basis of such variations. The present study was carried out to understand the mechanisms underlying radiation resistance during life stages of D. melanogaster. Homogenates from all the life stages of D. melanogaster were prepared at stipulated age. These homogenates were used for the determination of (1) enzymatic antioxidants: superoxide dismutase (SOD), catalase, D. melanogaster glutathione peroxidase (DmGPx), and glutathione S-transferase (GST); (2) reducing non-enzymatic antioxidants: total antioxidant capacity (TAC), reduced glutathione (GSH) and non-reducing non-enzymatic antioxidant trehalose; and (3) levels of protein carbonyl (PC) content. Age-dependent changes in radiation resistance and associated biochemical changes were also studied in young (2 d) and old (20 and 30 d) flies. TAC and GSH were found high in the early pupal stage, whereas catalase and DmGPx were found to increase in the early pupal stage. The non-feeding third instar (NFTI) larvae were found to have high levels of SOD and GST, besides NFTI larvae showed high levels of trehalose. A remarkable decrease was observed in radiation resistance and trehalose levels during the early pupal stage. The PC level was the highest during early pupal stage and was the lowest in NFTI larvae. Older flies showed high level of PC compared with young flies. In vitro increments in trehalose concentration correspond to reduced formation of PCs, suggesting a protective role of trehalose against free radicals. A strong correlation between levels of trehalose and PC formation suggests amelioration of proteome damage due to ionizing radiation (IR). Stages with high trehalose levels showed protected proteome and high radiation resistance, suggesting a

  11. Optogenetic pacing in Drosophila melanogaster (Conference Presentation)

    Science.gov (United States)

    Alex, Aneesh; Li, Airong; Men, Jing; Jerwick, Jason; Tanzi, Rudolph E.; Zhou, Chao

    2016-03-01

    A non-invasive, contact-less cardiac pacing technology can be a powerful tool in basic cardiac research and in clinics. Currently, electrical pacing is the gold standard for cardiac pacing. Although highly effective in controlling the cardiac function, the invasive nature, non-specificity to cardiac tissues and possible tissue damage limits its capabilities. Optical pacing of heart is a promising alternative, which is non-invasive and more specific, has high spatial and temporal precision, and avoids shortcomings in electrical stimulation. Optical coherence tomography has been proved to be an effective technique in non-invasive imaging in vivo with ultrahigh resolution and imaging speed. In the last several years, non-invasive specific optical pacing in animal hearts has been reported in quail, zebrafish, and rabbit models. However, Drosophila Melanogaster, which is a significant model with orthologs of 75% of human disease genes, has rarely been studied concerning their optical pacing in heart. Here, we combined optogenetic control of Drosophila heartbeat with optical coherence microscopy (OCM) technique for the first time. The light-gated cation channel, channelrhodopsin-2 (ChR2) was specifically expressed by transgene as a pacemaker in drosophila heart. By stimulating the pacemaker with 472 nm pulsed laser light at different frequencies, we achieved non-invasive and more specific optical control of the Drosophila heart rhythm, which demonstrates the wide potential of optical pacing for studying cardiac dynamics and development. Imaging capability of our customized OCM system was also involved to observe the pacing effect visually. No tissue damage was found after long exposure to laser pulses, which proved the safety of optogenetic control of Drosophila heart.

  12. External control of the Drosophila melanogaster egg to imago development period by specific combinations of 3D low-frequency electric and magnetic fields.

    Science.gov (United States)

    Makarov, Vladimir I; Khmelinskii, Igor

    2016-01-01

    We report that the duration of the egg-to-imago development period of the Drosophila melanogaster, and the imago longevity, are both controllable by combinations of external 3-dimensional (3D) low-frequency electric and magnetic fields (LFEMFs). Both these periods may be reduced or increased by applying an appropriate configuration of external 3D LFEMFs. We report that the longevity of D. melanogaster imagoes correlates with the duration of the egg-to-imago development period of the respective eggs. We infer that metabolic processes in both eggs and imago are either accelerated (resulting in reduced time periods) or slowed down (resulting in increased time periods). We propose that external 3D LFEMFs induce electric currents in live systems as well as mechanical vibrations on sub-cell, whole-cell and cell-group levels. These external fields induce media polarization due to ionic motion and orientation of electric dipoles that could moderate the observed effects. We found that the longevity of D. melanogaster imagoes is affected by action of 3D LFEMFs on the respective eggs in the embryonic development period (EDP). We interpret this effect as resulting from changes in the regulation mechanism of metabolic processes in D. melanogaster eggs, inherited by the resulting imagoes. We also tested separate effects of either 3D electric or 3D magnetic fields, which were significantly weaker.

  13. Light-induced vitamin deficiency in Drosophila melanogaster.

    Science.gov (United States)

    Bruins, B G; Scharloo, W; Thörig, G E

    1997-01-01

    Illumination by visible light (400 Ix) of cultures containing larvae of Drosophila melanogaster can reduce survival (Bruins et al., Insect Biochemistry 21:535-539, 1991). Here we show that the effect of light depends on the presence of propionic or acetic acid in the food medium. We also show that survival is far more affected by illumination of the yeast food media than by direct illumination of the eggs and developing larvae. It is shown that addition of antioxidants to the food prevents light induced mortality. The action of antioxidants suggests that free radicals are important in light induced mortality. We also showed that both yeast and riboflavin (vitamin B2) solutions illuminated with visible light (400 Ix) generate hydrogen peroxide. Other vitamin and amino acid solutions do not produce peroxide in measurable amounts. However, the concentration of photogenerated hydrogen peroxide is far too low to explain the death of eggs and developing larvae upon exposure to light. A 400 Ix light treatment destroys the capability of yeast food media to support survival of larvae. Addition of vitamin C, carotene, tryptophan, nipagin, uric acid, or sucrose to the light treated medium does not restore viability. It is restored when riboflavin is added to the photo-inactivated yeast. A high concentration of pyridoxine also produced an improvement in survival. When riboflavin is treated with light, it cannot support survival on synthetic food media nor can it restore survival on light treated yeast food media. These results show that riboflavin (or a derivative) is a major light sensitive compound of yeast, which can be degraded by light. Light induced loss of riboflavin leads to mortality, because this is an essential dietary vitamin. The vitamin degradation can be prevented by dietary antioxidants. A chromatographic analysis confirms this conclusion.

  14. Parathyroid hormone: Data mining for age-related reference intervals in adults.

    Science.gov (United States)

    Farrell, Christopher-John L; Nguyen, Lan; Carter, Andrew C

    2018-02-01

    Age-related changes in parathyroid hormone (PTH) have been previously documented in adults. However, because of the limitations of traditional approaches to establishing reference intervals, age-related reference intervals have not been defined. We sought to use a data mining approach to derive age-related PTH reference intervals. Results from patients undergoing PTH testing over a 4-year period were extracted from the database of a private pathology laboratory in New South Wales, Australia. Patients were included in the study if they were 18 years or older and had simultaneous determination of PTH, serum calcium, estimated glomerular filtration rate and 25-hydroxyvitamin D (25-OHD). Patients with abnormalities of serum calcium or renal function were excluded. Bhattacharya analysis of log-transformed data was used to derive age-related PTH reference intervals across adulthood. Results were available for 33 652 subjects. Among patients with optimal 25-OHD status, older age was associated with higher PTH concentrations. Age-related reference intervals were derived and showed a 63% increase in the upper and lower reference limits between the youngest (18-29 years of age) and the oldest (80 years of age or older) age partitions. The appropriateness of using a single reference interval for patients of all ages was evaluated against objective criteria and was found to be unsatisfactory. Data mining was demonstrated to be a useful tool for establishing age-related PTH reference intervals. The technique demonstrated that increasing age is associated with higher PTH concentrations and that age-related reference intervals are important for accurate result interpretation. © 2017 John Wiley & Sons Ltd.

  15. Age-related attitudes: the influence on relationships and performance at work.

    Science.gov (United States)

    Gellert, Franz Josef; Schalk, René

    2012-01-01

    This paper aims to examine the influence of age and age-related attitudes on relationship factors. In addition, it seeks to assess how both factors affect care service work performance. The paper explores the influence of age and age-related attitudes on the relationship quality among employees, affecting performance in mentally and physically demanding work settings. The authors conducted the research in six residential homes for the elderly in Germany (152 respondents) and collected the data with questionnaires. Data are analyzed by multi-hierarchical regression analyses. Results show that age-related attitudes (intergenerational cooperation and the perception of older employees' capabilities) are important factors influencing the perceived quality level of in-group cooperation. Both age-related attitudes and relationship factors influence perceived employee performance, and job satisfaction. The findings contribute to understanding how age-related attitudes influence relationships among employees, the relationship between employees and supervisor, and the effect on service performance. The mono-cultural sample might be a limitation, as well as the composition of the sample: The majority of respondents were female. For leaders, supervisors and managers the results contribute to understanding how employees' age-related attitudes, in mentally and physically demanding work settings, influence the quality level of relationships and outcomes. This is relevant in the context of leaders/supervisors promoting followers' individual development and group/team development. The paper shows that in care service work with an increasing number of older employees, the positive perception of age-related attitudes influences relationship quality and performance positively.

  16. Nurse-led ranibizumab intravitreal injections in wet age-related macular degeneration: a literature review.

    Science.gov (United States)

    Gregg, Emma

    2017-04-12

    Aim The aim of this literature review was to explore the development of the role of specialist ophthalmic nurses in delivering ranibizumab intravitreal injections to patients with wet age-related macular degeneration (AMD), and to evaluate their contribution to reducing capacity pressures in medical retina services, while maintaining safe and effective standards of care. Method A systematic literature search was undertaken to identify relevant articles published between January 2000 and June 2015. A search of electronic databases was undertaken, and selected relevant journals were searched manually. A free text and subject heading search strategy was conducted, in which the abstracts of publications identified for review were assessed for relevance. Inclusion criteria were: nurses delivering ranibizumab intravitreal treatment; studies performed in the UK and other countries; and patients with AMD, diabetic macular oedema or central retinal vein occlusion receiving nurse-led ranibizumab (Lucentis) intravitreal treatment. Findings Five studies were identified from the literature search, which audited a total of 31,303 injections delivered by nurse practitioners between January 2007 and November 2013. The visual outcomes and the rate of complications from intravitreal injections delivered by trained ophthalmic nurse practitioners were comparable to intravitreal injections delivered by ophthalmologists. Four of the five studies reported increased patient satisfaction, patients consenting to nurse-delivered intravitreal injections, favourable pain experience, and absence of complaints. Conclusion Practice innovation is an example of a quality, innovation, productivity and prevention process. Role expansion, in which specialist ophthalmic nurses deliver intravitreal injections, has been shown to be economical, safe and effective. It enables timely delivery of the service, thereby preventing irreversible blindness for individuals with wet AMD.

  17. Calorie restriction: A new therapeutic intervention for age-related dry eye disease in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kawashima, Motoko; Kawakita, Tetsuya; Okada, Naoko; Ogawa, Yoko [Department of Ophthalmology, Keio University School of Medicine, Tokyo (Japan); Murat, Dogru [Department of Ocular Surface and Visual Optics, Keio University School of Medicine, Tokyo (Japan); Nakamura, Shigeru; Nakashima, Hideo [Research Center, Ophtecs Corporation, Hyogo (Japan); Shimmura, Shigeto [Department of Ophthalmology, Keio University School of Medicine, Tokyo (Japan); Shinmura, Ken [Division of Geriatric Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan); Tsubota, Kazuo, E-mail: tsubota@sc.itc.keio.ac.jp [Department of Ophthalmology, Keio University School of Medicine, Tokyo (Japan)

    2010-07-09

    A decrease in lacrimal gland secretory function is closely related to aging and leads to an increased prevalence of dry eye syndrome. Since calorie restriction (CR) is considered to prevent functional decline of various organs due to aging, we hypothesized that CR could prevent age-related lacrimal dysfunction. Six-month-old male Fischer 344 rats were randomly divided into ad libitum (AL) and CR (-35%) groups. After 6 months of CR, tear function was examined under conscious state. After euthanasia, lacrimal glands were subjected to histological examination, tear protein secretion stimulation test with Carbachol, and assessment of oxidative stress with 8-hydroxy-2 deoxyguanosine (8-OHdG) and 4-hydroxynonenal (HNE) antibodies. CR significantly improved tear volume and tended to increase tear protein secretion volume after stimulation with Carbachol compared to AL. The acinar unit density was significantly higher in the CR rats compared to AL rats. Lacrimal glands in the CR rats showed a lesser degree of interstitial fibrosis. CR reduced the concentration of 8-OHdG and the extent of staining with HNE in the lacrimal gland, compared to AL. Furthermore, our electron microscopic observations showed that mitochondrial structure of the lacrimal gland obtained from the middle-aged CR rats was preserved in comparison to the AL rats. Collectively, these results demonstrate for the first time that CR may attenuate oxidative stress related damage in the lacrimal gland with preservation of lacrimal gland functions. Although molecular mechanism(s) by which CR maintains lacrimal gland function remains to be resolved, CR might provide a novel therapeutic strategy for treating dry eye syndrome.

  18. Calorie restriction: A new therapeutic intervention for age-related dry eye disease in rats

    International Nuclear Information System (INIS)

    Kawashima, Motoko; Kawakita, Tetsuya; Okada, Naoko; Ogawa, Yoko; Murat, Dogru; Nakamura, Shigeru; Nakashima, Hideo; Shimmura, Shigeto; Shinmura, Ken; Tsubota, Kazuo

    2010-01-01

    A decrease in lacrimal gland secretory function is closely related to aging and leads to an increased prevalence of dry eye syndrome. Since calorie restriction (CR) is considered to prevent functional decline of various organs due to aging, we hypothesized that CR could prevent age-related lacrimal dysfunction. Six-month-old male Fischer 344 rats were randomly divided into ad libitum (AL) and CR (-35%) groups. After 6 months of CR, tear function was examined under conscious state. After euthanasia, lacrimal glands were subjected to histological examination, tear protein secretion stimulation test with Carbachol, and assessment of oxidative stress with 8-hydroxy-2 deoxyguanosine (8-OHdG) and 4-hydroxynonenal (HNE) antibodies. CR significantly improved tear volume and tended to increase tear protein secretion volume after stimulation with Carbachol compared to AL. The acinar unit density was significantly higher in the CR rats compared to AL rats. Lacrimal glands in the CR rats showed a lesser degree of interstitial fibrosis. CR reduced the concentration of 8-OHdG and the extent of staining with HNE in the lacrimal gland, compared to AL. Furthermore, our electron microscopic observations showed that mitochondrial structure of the lacrimal gland obtained from the middle-aged CR rats was preserved in comparison to the AL rats. Collectively, these results demonstrate for the first time that CR may attenuate oxidative stress related damage in the lacrimal gland with preservation of lacrimal gland functions. Although molecular mechanism(s) by which CR maintains lacrimal gland function remains to be resolved, CR might provide a novel therapeutic strategy for treating dry eye syndrome.

  19. Swimming exercise reverses aging-related contractile abnormalities of female heart by improving structural alterations.

    Science.gov (United States)

    Ozturk, Nihal; Olgar, Yusuf; Er, Hakan; Kucuk, Murathan; Ozdemir, Semir

    2017-01-01

    The objective of this study was to examine the effect of swimming exercise on aging-related Ca2+ handling alterations and structural abnormalities of female rat heart. For this purpose, 4-month and 24-month old female rats were used and divided into three following groups: sedentary young (SY), sedentary old (SO), and exercised old (Ex-O). Swimming exercise was performed for 8 weeks (60 min/day, 5 days/week). Myocyte shortening, L-type Ca2+ currents and associated Ca2+ transients were measured from ventricular myocytes at 36 ± 1°C. NOX-4 levels, aconitase activity, glutathione measurements and ultrastructural examination by electron microscopy were conducted in heart tissue. Swimming exercise reversed the reduced shortening and slowed kinetics of aged cardiomyocytes. Although the current density was similar for all groups, Ca2+ transients were higher in SO and Ex-O myocytes with respect to the SY group. Caffeine-induced Ca2+ transients and the integrated NCX current were lower in cardiomyocytes of SY rats compared with other groups, suggesting an increased sarcoplasmic reticulum Ca2+ content in an aged heart. Aging led to upregulated cardiac NOX-4 along with declined aconitase activity. Although it did not reverse these oxidative parameters, swimming exercise achieved a significant increase in glutathione levels and improved structural alterations of old rats' hearts. We conclude that swimming exercise upregulates antioxidant defense capacity and improves structural abnormalities of senescent female rat heart, although it does not change Ca2+ handling alterations further. Thereby, it improves contractile function of aged myocardium by mitigating detrimental effects of oxidative stress.

  20. Melatonin: Antioxidant and modulatory properties in age-related changes during Trypanosoma cruzi infection.

    Science.gov (United States)

    Brazão, Vânia; Santello, Fabricia H; Colato, Rafaela P; Mazotti, Tamires T; Tazinafo, Lucas F; Toldo, Míriam Paula A; do Vale, Gabriel T; Tirapelli, Carlos R; do Prado, José C

    2017-08-01

    The purpose of this study was to investigate the effects of melatonin on selected biomarkers of innate and humoral immune response as well as the antioxidant/oxidant status (superoxide dismutase-SOD and reduced glutathione levels (GSH) to understand whether age-related changes would influence the development of acute Trypanosoma cruzi (T. cruzi) infection. Young- (5 weeks) and middle-aged (18 months) Wistar rats were orally treated with melatonin (gavage) (05 mg/kg/day), 9 days after infection. A significant increase in both SOD activity and GSH levels was found in plasma from all middle-aged melatonin-treated animals. Melatonin triggered enhanced expression of major histocompatibility class II (MHC-II) antigens on antigen-presenting cell (APC) and peritoneal macrophages in all treated animals. High levels of CD4 + CD28-negative T cells (*PMelatonin induced a significant reduction (***PMelatonin also triggered an upregulation of CD80 and CD86 expression in all young-treated groups. Significant percentages of B and spleen dendritic cells in middle-aged infected and treated animals were observed. Our data reveal new features of melatonin action in inhibiting membrane lipid peroxidation, through the reduction in 8-isoprostane, upregulating the antioxidant defenses and triggering an effective balance in the antioxidant/oxidant status during acute infection. The ability of melatonin to counteract the immune alterations induced by aging added further support to its use as a potential therapeutic target not only for T. cruzi infection but also for other immunocompromised states. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Biomarkers of oxidative stress in patients with wet age related macular degeneration.

    Science.gov (United States)

    Zafrilla, P; Losada, M; Perez, A; Caravaca, G; Mulero, J

    2013-03-01

    The aim of this study was to analyze biomarkers of oxidative stress in patients with wet age related macular degeneration (AMD). Case-control study that includes 163 patients with wet AMD (age group of 55-82 years with the mean age of 71 years and 170 age-matched healthy controls in the age group of 55-78 years with the mean age of 71 years. The following parameters were determined: reduced and oxidized Glutathione (GSH/GSSH), protein carbonyl groups, total antioxidant activity in plasma and the activity of endogenous antioxidant enzymes, such as, gluthatione peroxidase, gluthatione reductase and superoxide dismutase. We observed total antioxidant activity higher in control group (CG) compared with patients with wet AMD (7.1 ± 1.2 μM Trolox vs 5.8 ± 1.1 μM Trolox). Values of superoxide dismutase activity (SOD), gluthatione reductase (GR) and gluthatione peroxidase (GPx) are higher in control group than in patients with wet AMD. According to the GSH/GSSH results, average values were higher in the CG than in patients with wet AMD and data were not significantly different.. Values of protein carbonyl groups were higher in patients with wet AMD than in CG and significant differences were found. The finding of the present study suggests that the patients with wet AMD are an altered metabolic state of oxidation-reduction and that it is convenient to give therapeutic interventions with antioxidants. We have demonstrated that systematic oxidative stress, measured by different biomarkers is closely associated with the wet AMD.

  2. Age-Related Deficits in Efficiency of Low-Level Lateral Inhibition

    Directory of Open Access Journals (Sweden)

    Friederike eSchlaghecken

    2012-04-01

    Full Text Available In a masked prime task using a 0-ms prime-target inter-stimulus-interval, responses on compatible trials (prime and target match are usually faster and more accurate than responses on incompatible trials (prime-target mismatch. This positive compatibility effect comprises benefits on compatible relative to neutral trials and costs on incompatible relative to neutral trials. Comparing performance in 2- vs. 4-alternative-response versions of the task indicates that benefits are due to direct priming of a motor response, whereas costs reflect inhibition of the alternative response tendency. The present study investigates whether normal aging is associated with a selective deficit in the inhibitory component, affecting both low-level motor and higher-level executive control. Testing 20 young and 20 older adults, we found that (a overall, prime-induced benefits were of similar magnitude across age groups, but inhibition-based costs were smaller in older compared to young adults; (b increasing the number of response alternatives caused the same pattern of unaltered benefits and reduced costs in both age groups; and (c costs, but not benefits, in the 2-alternative condition were significantly predicted by scores on the digit-symbol substitution task (DSST, independently of age and other background variables. Results demonstrate the possibility of isolating an inhibitory component in low-level perceptuo-motor control. Importantly, this component shows an age-related decline in the absence of a corresponding decline of visuo-motor excitability, and appears to be linked to performance on a higher-level processing speed task. We hypothesize that aging might affect the brain's ability to establish precise short-term lateral inhibitory links, and that even in young adults, the efficiency of such links is a significant contributing factor in higher-level cognitive performance.

  3. Localization of age-related macular degeneration-associated ARMS2 in cytosol, not mitochondria

    Science.gov (United States)

    Wang, Gaofeng; Spencer, Kylee L.; Court, Brenda L.; Olson, Lana M.; Scott, William K.; Haines, Jonathan L.; Pericak-Vance, Margaret A.

    2010-01-01

    PURPOSE To analyze the relationship between ARMS2 and HTRA1 in the association with age-related macular degeneration (AMD) in an independent case-control dataset, and to investigate the subcellular localization of the ARMS2 protein in an in vitro system. METHOD Two SNPs in ARMS2 and HTRA1 were genotyped in 685 cases and 269 controls by Taqman Assay. Allelic association was tested by a χ2 test. A likelihood ratio test (LRT) of full vs. reduced models was utilized to analyze the interaction between ARMS2 and smoking and HTRA1 and smoking, after adjusting for CFH and age. Immunofluorescence and immunoblot were applied to localize ARMS2 in retinal epithelial ARPE-19 cells and COS7 cell transfected by ARMS2 constructs. RESULT Both significantly associated SNP rs10490924 and rs11200638 (P<0.0001) are in strong linkage disequilibrium (LD) (D′=0.97, r2=0.93) that generates virtually identical association test and odds ratios. In separate logistic regression models the interaction effect for both smoking with ARMS2 and with HTRA1 was not statistically significant. Immunofluorescence and immunoblot show that both endogenous and exogenous ARMS2 are mainly distributed in the cytosol, not the mitochondria. Comparing to wild type, ARMS2 A69S is more likely to be associated with cytoskeleton in COS7 cells. CONCLUSIONS The significant associations in ARMS2 and HTRA1 are with polymorphisms in strong LD that confer virtually identical risks, preventing differentiation at the statistical level. We found that ARMS2 was mainly distributed in the cytosol, not in mitochondrial outer membrane as previously reported, suggesting that ARMS2 may not confer risk to AMD through the mitochondrial pathway. PMID:19255159

  4. OCT-Angiography for monitoring and managing neovascular age-related macular degeneration.

    Science.gov (United States)

    Malamos, P; Tsolkas, G; Kanakis, M; Mylonas, G; Karatzenis, D; Oikonomopoulos, N; Lakoumentas, J; Georgalas, Ilias

    2017-12-01

    To evaluate the combined use of optical coherence tomography and angiography (OCT-A) for imaging choroidal neovascularization (CNV) secondary to neovascular age-related macular degeneration (nAMD). This prospective observational study was conducted from May 2015 to April 2017. Included in the study were 54 patients (n = 63 eyes), all of whom had CNV secondary to nAMD and all of whom had been examined by OCT-A. Angioscans (3x3 and 6 × 6) and conventional B-scan OCT scans were obtained for all patients at baseline and at various times during the 24-month follow-up period. For diagnostic confirmation, conventional imaging methods fluorescein angiography (FA) and indocyanine green angiography (ICGA) were performed at baseline. A total of 13 patients (n = 15 eyes) underwent serial imaging during 34 follow-up visits. The main outcomes included (i) determination of OCT-A sensitivity for the detection of CNV (classic and occult) and (ii) the correlation between B-scan OCT and OCT-A vis-à-vis consecutive follow-up changes. At baseline, the detection rate (i.e., overall sensitivity) of OCT-A for detecting CNV was 64.4% (75.7 and 48.0% for classic and occult CNV, respectively), independent of prior treatment status. In terms of quality, 6 × 6 angioscans were superior to 3 × 3. Moreover, specific CNV morphologic patterns by B-scan OCT did not correlate with lesion composition. Correspondence between OCT-A and B-scan OCT was observed in only 53% of the cases. OCT-A may prove to be a valuable adjunctive diagnostic tool for the interpretation of CNV, as it not only reduces the need for invasive angiographic procedures but also facilitates the follow-up process.

  5. ADAPTIVE OPTICS IMAGING OF FOVEAL SPARING IN GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Querques, Giuseppe; Kamami-Levy, Cynthia; Georges, Anouk; Pedinielli, Alexandre; Capuano, Vittorio; Blanco-Garavito, Rocio; Poulon, Fanny; Souied, Eric H

    2016-02-01

    To describe adaptive optics (AO) imaging of foveal sparing in geographic atrophy (GA) secondary to age-related macular degeneration. Flood-illumination AO infrared (IR) fundus images were obtained in four consecutive patients with GA using an AO retinal camera (rtx1; Imagine Eyes). Adaptive optics IR images were overlaid with confocal scanning laser ophthalmoscope near-IR autofluorescence images to allow direct correlation of en face AO features with areas of foveal sparing. Adaptive optics appearance of GA and foveal sparing, preservation of functional photoreceptors, and cone densities in areas of foveal sparing were investigated. In 5 eyes of 4 patients (all female; mean age 74.2 ± 11.9 years), a total of 5 images, sized 4° × 4°, of foveal sparing visualized on confocal scanning laser ophthalmoscope near-IR autofluorescence were investigated by AO imaging. En face AO images revealed GA as regions of inhomogeneous hyperreflectivity with irregularly dispersed hyporeflective clumps. By direct comparison with adjacent regions of GA, foveal sparing appeared as well-demarcated areas of reduced reflectivity with less hyporeflective clumps (mean 14.2 vs. 3.2; P = 0.03). Of note, in these areas, en face AO IR images revealed cone photoreceptors as hyperreflective dots over the background reflectivity (mean cone density 3,271 ± 1,109 cones per square millimeter). Microperimetry demonstrated residual function in areas of foveal sparing detected by confocal scanning laser ophthalmoscope near-IR autofluorescence. Adaptive optics allows the appreciation of differences in reflectivity between regions of GA and foveal sparing. Preservation of functional cone photoreceptors was demonstrated on en face AO IR images in areas of foveal sparing detected by confocal scanning laser ophthalmoscope near-IR autofluorescence.

  6. A preliminary comparative treatment planning study for radiotherapy of age-related maculopathy

    International Nuclear Information System (INIS)

    Mazal, A.; Schwartz, L.; Lacroix, F.; Mammar, H.; Delacroix, S.; Ferrand, R.; Nauraye, C.; Desjardins, L.; Schlienger, P.; D'Hermies, F.; Frau, E.; Habrand, J.-L.; Rosenwald, J.-C.

    1998-01-01

    Purpose: We present a comparative planning of different approaches for external radiotherapy in age-related maculopathies. Materials and methods: Calculated dose distributions and dose-volume histograms for (a) bilateral irradiation with 6 MV photons, (b) a single lateral-oblique beam using either photons, electrons or protons and (c) an anterior circular proton beam. Results: For lateral photon or electron beams the dose to the lens is usually lower than 10% of the dose to the macula. The entrance doses for bilateral photon beams are about 50% which increase up to 100% at the orbital bone. About 5 mm of optic nerves are irradiated at the maximal dose while the optic chiasma is spared. A single photon beam gives 50% of the dose to the fellow eye. The electron beam spares the fellow eye but gives a rather inhomogeneous dose to the target volume. For a lateral proton beam, 4 mm of optic nerve receives 90% of the dose, the skin dose is at least 70% of the dose to the macula and the lens and the fellow eye are spared. An anterior proton beam gives 90% of the dose to 1 mm of optic nerve and the 50% isodose approaches the periphery of the lens. Conclusion: Doses to the critical structures can be dramatically diminished for all the techniques by reducing the beam size, but only if very precise set-up techniques are used. Proton beams are an attractive solution, but the impact of such a choice on the use of proton facilities and on the national health system should be carefully evaluated, as well as the risk of radio-induced secondary neoplasias. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  7. Vitamin E and risk of age-related cataract: a meta-analysis.

    Science.gov (United States)

    Zhang, Yufei; Jiang, Wenjie; Xie, Zhutian; Wu, Wenlong; Zhang, Dongfeng

    2015-10-01

    We conducted a meta-analysis to evaluate the relationship between vitamin E and age-related cataract (ARC). The fixed- or random-effect model was selected based on heterogeneity. Meta-regression was used to explore potential sources of between-study heterogeneity. Publication bias was evaluated using Begg's test. The dose-response relationship was assessed by a restricted cubic spline model. Relevant studies were identified by a search of PubMed and the Cochrane Library to May 2014, without language restrictions. Studies involved samples of people of all ages. Dietary vitamin E intake, dietary and supplemental vitamin E intake, and high serum tocopherol levels were significantly associated with decreased risk of ARC, the pooled relative risk was 0·73 (95% CI 0·58, 0·92), 0·86 (95% CI 0·75, 0·99) and 0·77 (95% CI 0·66, 0·91), respectively. Supplemental vitamin E intake was non-significantly associated with ARC risk (relative risk=0·92; 95% CI 0·78, 1·07). The findings from dose-response analysis showed evidence of a non-linear association between dietary vitamin E intake and ARC. The risk of ARC decreased with dietary vitamin E intake from 7 mg/d (relative risk=0·94; 95% CI 0·90, 0·97). The findings of the meta-analysis indicated that dietary vitamin E intake, dietary and supplemental vitamin E intake, and high level of serum tocopherol might be significantly associated with reduced ARC risk.

  8. Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components

    International Nuclear Information System (INIS)

    Tashiro, Kanae; Shishido, Mayumi; Fujimoto, Keiko; Hirota, Yuko; Yo, Kazuyuki; Gomi, Takamasa; Tanaka, Yoshitaka

    2014-01-01

    Highlights: •Autophagosomes accumulate in aged dermal fibroblasts. •Autophagic degradation is impaired in aged dermal fibroblasts. •Autophagy disruption affects extracellular matrix components in dermal fibroblasts. -- Abstract: Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Western blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5—genes essential for autophagosome formation—was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility

  9. [Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

    Science.gov (United States)

    Fischer, Tamás

    2015-11-15

    It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors

  10. Effect of Hawthorn on Drosophila Melanogaster Antioxidant-Related ...

    African Journals Online (AJOL)

    Purpose: To study the effects of various doses of hawthorn extract on Drosophila lifespan, antioxidant enzyme activity and expression of antioxidant-related regulation genes. Methods: Experiments with Drosophila as an animal model were conducted. The effects of hawthorn on Drosophila melanogaster antioxidant related ...

  11. Latitudinal clines in Drosophila melanogaster: body size, allozyme ...

    Indian Academy of Sciences (India)

    Unknown

    latitude temperate populations of D. melanogaster (Eanes. 1999; Verrelli and Eanes 2001b). It is surmised that the higher ADH and α-GPDH activities facilitate lipid stor- age. Higher lipid storage might increase longevity or fecundity. Higher PGM activity is strongly related to higher glycogen content in adult flies (Verrelli and ...

  12. Latitudinal clines in Drosophila melanogaster: body size, allozyme ...

    Indian Academy of Sciences (India)

    It is argued that adult body size clines, inversion frequency clines, and clines in allele frequency at loci involved in glycolysis and glycogen storage are part of the same adaptive strategy. Selection pressure is expected to differ at opposite ends of the clines. At high latitudes, selection on D. melanogaster would favour high ...

  13. Latitudinal clines in Drosophila melanogaster: body size, allozyme ...

    Indian Academy of Sciences (India)

    Unknown

    Body size may be measured as fresh weight, wing length, wing area or thorax length. .... starvation resistance. Indeed, a latitudinal cline for star- vation resistance and desiccation resistance is present in. Indian populations of D. melanogaster (Karan et al. 1998). ..... 215 effects. Loss-of-function mutations in any of the insulin-.

  14. DIRECT SELECTION ON LIFE-SPAN IN DROSOPHILA-MELANOGASTER

    NARCIS (Netherlands)

    ZWAAN, B; BIJLSMA, R; HOEKSTRA, RE

    An important issue in the study of the evolution of aging in Drosophila melanogaster is whether decreased early fecundity is inextricably coupled with increased life span in selection experiments on age at reproduction. Here, this problem has been tackled using an experimental design in which

  15. Geographical analysis of diapause inducibility in European Drosophila melanogaster populations.

    Science.gov (United States)

    Pegoraro, Mirko; Zonato, Valeria; Tyler, Elizabeth R; Fedele, Giorgio; Kyriacou, Charalambos P; Tauber, Eran

    2017-04-01

    Seasonal overwintering in insects represents an adaptation to stressful environments and in European Drosophila melanogaster females, low temperatures and short photoperiods can induce an ovarian diapause. Diapause may represent a recent (melanogaster from tropical sub-Saharan Africa, because African D. melanogaster and the sibling species D. simulans, have been reported to fail to undergo diapause. Over the past few centuries, D. melanogaster have also invaded North America and Australia, and eastern populations on both continents show a predictable latitudinal cline in diapause induction. In Europe however, a new diapause-enhancing timeless allele, ls-tim, is observed at high levels in southern Italy (∼80%), where it appears to have arisen and has spread throughout the continent with a frequency of ∼20% in Scandinavia. Given the phenotype of ls-tim and its geographical distribution, we might predict that it would work against any latitudinal cline in diapause induction within Europe. Indeed we reveal that any latitudinal cline for diapause in Europe is very weak, as predicted by ls-tim frequencies. In contrast, we determine ls-tim frequencies in North America and observe that they would be expected to strengthen the latitudinal pattern of diapause. Our results reveal how a newly arisen mutation, can, via the stochastic nature of where it initially arose, blur an otherwise adaptive geographical pattern. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Nearly Neutral Evolution Across the Drosophila melanogaster Genome

    DEFF Research Database (Denmark)

    Esteve, David Castellano; James, Jennifer; Eyre-Walker, Adam

    2017-01-01

    Under the nearly neutral theory of molecular evolution the proportion of effectively neutral mutations is expected to depend upon the effective population size (Ne). Here we investigate whether this is the case across the genome of Drosophila melanogaster using polymorphism data from 128 North...

  17. P element excision in drosophila melanogaster and related drosophilids

    Science.gov (United States)

    The frequency of P element excision and the structure of the resulting excision products were determined in three drosophilid species, Drosophila melanogaster, D. virilis, and Chymomyza procnemis. A transient P element mobility assay was conducted in the cells of developing insect embryos, but unlik...

  18. mutations of Drosophila melanogaster cause nonrandom cell death ...

    Indian Academy of Sciences (India)

    In Drosophila melanogaster, the intersex (ix) is a terminally positioned gene in somatic sex determination hierarchy and function with the female specific product of double sex (DSXF) to implement female sexual differentiation. The null phenotype of ix is to transform diplo-X individuals into intersexes while leaving haplo-X ...

  19. Ionizing radiation causes the stress response in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Gruntenko, N.E.; Zakharenko, L.P.; Raushenbakh, I.Yu.

    1998-01-01

    Potentiality of the stress-reaction arising in Drosophila melanogaster under gamma-irradiation of the source with 137 Cs (irradiation dose is 10 Gy , radiation dose rate amounts 180 c Gy/min) is studied. It is shown that radiation induces the stress-reaction in Drosophila resulting in alterations in energetic metabolism (biogenic amines metabolic system) and in reproductive function [ru

  20. Inbreeding affects locomotor activity in Drosophila melanogaster at different ages

    DEFF Research Database (Denmark)

    Manenti, Tommaso; Pertoldi, Cino; Nasiri Moghadam, Neda

    2015-01-01

    The ability to move is essential for many behavioural traits closely related to fitness. Here we studied the effect of inbreeding on locomotor activity (LA) of Drosophila melanogaster at different ages under both dark and light regimes. We expected to find a decreased LA in inbred lines compared...

  1. Characterization of reproductive dormancy in male Drosophila melanogaster

    Czech Academy of Sciences Publication Activity Database

    Kubrak, O. I.; Kučerová, Lucie; Theopold, U.; Nylin, S.; Nässel, D. R.

    2016-01-01

    Roč. 7, NOV 24 (2016), č. článku 572. ISSN 1664-042X Institutional support: RVO:60077344 Keywords : Drosophila melanogaster * diapause * reproduction Subject RIV: ED - Physiology Impact factor: 4.134, year: 2016 http://journal.frontiersin.org/article/10.3389/fphys.2016.00572/full

  2. Aging assessment of reactor instrumentation and protection system components. Aging-related operating experiences

    Energy Technology Data Exchange (ETDEWEB)

    Gehl, A.C.; Hagen, E.W. [Oak Ridge National Lab., TN (United States)

    1992-07-01

    A study of the aging-related operating experiences throughout a five-year period (1984--1988) of six generic instrumentation modules (indicators, sensors, controllers, transmitters, annunciators, and recorders) was performed as a part of the Nuclear Plant Aging Research Program. The effects of aging from operational and environmental stressors were characterized from results depicted in Licensee Event Reports (LERs). The data are graphically displayed as frequency of events per plant year for operating plant ages from 1 to 28 years to determine aging-related failure trend patterns. Three main conclusions were drawn from this study: (1) Instrumentation and control (I&C) modules make a modest contribution to safety-significant events: 17% of LERs issued during 1984--1988 dealt with malfunctions of the six I&C modules studied, and 28% of the LERs dealing with these I&C module malfunctions were aging related (other studies show a range 25--50%); (2) Of the six modules studied, indicators, sensors, and controllers account for the bulk (83%) of aging-related failures; and (3) Infant mortality appears to be the dominant aging-related failure mode for most I&C module categories (with the exception of annunciators and recorders, which appear to fail randomly).

  3. A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer's Disease.

    Science.gov (United States)

    Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

    2016-01-01

    Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer's Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer's Disease.

  4. Neural and non‐neural contributions to sexual dimorphism of mid‐day sleep in Drosophila melanogaster: a pilot study

    Science.gov (United States)

    Khericha, Mobina; Kolenchery, Jaison B.

    2016-01-01

    Abstract Many of the characteristics associated with mammalian sleep are also observed in Drosophila melanogaster Meigen, making the fruit fly a powerful model organism for studying the genetics of this important process. Included among the similarities is the presence of sexual dimorphic sleep patterns, which, in flies, are manifested as increased mid‐day sleep (‘siesta’) in males compared with females. In the present study, targeted mis‐expression of the genes transformer (tra) and tra2 is used to either feminize or masculinize specific neural and non‐neural tissues in the fly. Feminization of male D. melanogaster using three different GAL4 drivers that are expressed in the mushroom bodies induces a female‐like reduced siesta, whereas the masculinization of females using these drivers triggers the male‐like increased siesta. A similar reversal of sex‐specific sleep is also observed by mis‐expressing tra in the fat body, which is a key tissue in energy metabolism and hormone secretion. In addition, the daily expression levels of takeout, an important circadian clock output gene, are sexually dimorphic. Taken together, these experiments suggest that sleep sexual dimorphism in D. melanogaster is driven by multiple neural and non‐neural circuits, within and outside the brain. PMID:27840547

  5. Visual Detection of Speckles in the Fish Xenotoca variata by the Predatory Snake Thamnophis melanogaster in Water of Different Turbidity.

    Science.gov (United States)

    Manjarrez, Javier; Rivas-González, Eric; Venegas-Barrera, Crystian S; Moyaho, Alejandro

    2015-01-01

    Semi-aquatic snakes integrate visual and chemical stimuli, and prey detection and capture success are therefore linked to the display of visual predatory behavior. The snake Thamnophis melanogaster responds preferentially to individuals of the fish Xenotoca variata with a greater number of bright, colorful spots (lateral speckles) compared with those with a smaller number; however, water turbidity can reduce underwater visibility and effect the vulnerability of fish. In this study, we tested whether the presence of iridescent speckles on the flanks of male X. variata interacted with water turbidity to modify the predatory behavior displayed by the snake T. melanogaster. We predicted that in an experimental laboratory test, the snakes would increase the frequency of their predatory behavior to the extent that the water turbidity decreases. The snakes were tested at six different levels of water turbidity, in combination with three categories of male fish (with few, a median number of, or many speckles). The results showed that in a pool with high or zero turbidity, the number of speckles is not a determining factor in the deployment of the predatory behavior of the snake T. melanogaster toward X. variata. Our findings suggest that snakes can view the fish at intermediate percentages of turbidity, but the number of speckles in male X. variata is irrelevant as an interspecific visual signal in environments with insufficient luminosity. The successful capture of aquatic prey is influenced by integration between chemical and visual signals, according to environmental factors that may influence the recognition of individual traits.

  6. Visual Detection of Speckles in the Fish Xenotoca variata by the Predatory Snake Thamnophis melanogaster in Water of Different Turbidity.

    Directory of Open Access Journals (Sweden)

    Javier Manjarrez

    Full Text Available Semi-aquatic snakes integrate visual and chemical stimuli, and prey detection and capture success are therefore linked to the display of visual predatory behavior. The snake Thamnophis melanogaster responds preferentially to individuals of the fish Xenotoca variata with a greater number of bright, colorful spots (lateral speckles compared with those with a smaller number; however, water turbidity can reduce underwater visibility and effect the vulnerability of fish. In this study, we tested whether the presence of iridescent speckles on the flanks of male X. variata interacted with water turbidity to modify the predatory behavior displayed by the snake T. melanogaster. We predicted that in an experimental laboratory test, the snakes would increase the frequency of their predatory behavior to the extent that the water turbidity decreases. The snakes were tested at six different levels of water turbidity, in combination with three categories of male fish (with few, a median number of, or many speckles. The results showed that in a pool with high or zero turbidity, the number of speckles is not a determining factor in the deployment of the predatory behavior of the snake T. melanogaster toward X. variata. Our findings suggest that snakes can view the fish at intermediate percentages of turbidity, but the number of speckles in male X. variata is irrelevant as an interspecific visual signal in environments with insufficient luminosity. The successful capture of aquatic prey is influenced by integration between chemical and visual signals, according to environmental factors that may influence the recognition of individual traits.

  7. RNAi validation of resistance genes and their interactions in the highly DDT-resistant 91-R strain of Drosophila melanogaster.

    Science.gov (United States)

    Gellatly, Kyle J; Yoon, Kyong Sup; Doherty, Jeffery J; Sun, Weilin; Pittendrigh, Barry R; Clark, J Marshall

    2015-06-01

    4,4'-dichlorodiphenyltrichloroethane (DDT) has been re-recommended by the World Health Organization for malaria mosquito control. Previous DDT use has resulted in resistance, and with continued use resistance will increase in terms of level and extent. Drosophila melanogaster is a model dipteran that has many available genetic tools, numerous studies done on insecticide resistance mechanisms, and is related to malaria mosquitoes allowing for extrapolation. The 91-R strain of D. melanogaster is highly resistant to DDT (>1500-fold), however, there is no mechanistic scheme that accounts for this level of resistance. Recently, reduced penetration, increased detoxification, and direct excretion have been identified as resistance mechanisms in the 91-R strain. Their interactions, however, remain unclear. Use of UAS-RNAi transgenic lines of D. melanogaster allowed for the targeted knockdown of genes putatively involved in DDT resistance and has validated the role of several cuticular proteins (Cyp4g1 and Lcp1), cytochrome P450 monooxygenases (Cyp6g1 and Cyp12d1), and ATP binding cassette transporters (Mdr50, Mdr65, and Mrp1) involved in DDT resistance. Further, increased sensitivity to DDT in the 91-R strain after intra-abdominal dsRNA injection for Mdr50, Mdr65, and Mrp1 was determined by a DDT contact bioassay, directly implicating these genes in DDT efflux and resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Intraocular lenses for the treatment of age-related cataracts: an evidence-based analysis.

    Science.gov (United States)

    2009-01-01

    The objective of the report is to examine the comparative effectiveness and cost-effectiveness of various intraocular lenses (IOLs) for the treatment of age-related cataracts. TARGET POPULATION AND CONDITION A cataract is a hardening and clouding of the normally transparent crystalline lens that may result in a progressive loss of vision depending on its size, location and density. The condition is typically bilateral, seriously compromises visual acuity and contrast sensitivity and increases glare. Cataracts can also affect people at any age, however, they usually occur as a part of the natural aging process. The occurrence of cataracts increases with age from about 12% at age 50 years, to 60% at age 70. In general, approximately 50% of people 65 year of age or older have cataracts. Mild cataracts can be treated with a change in prescription glasses, while more serious symptoms are treated by surgical removal of the cataract and implantation of an IOL. In Ontario, the estimated prevalence of cataracts increased from 697,000 in 1992 to 947,000 in 2004 (35.9% increase, 2.4% annual increase). The number of cataract surgeries per 1,000 individuals at risk of cataract increased from 64.6 in 1992 to 140.4 in 1997 (61.9% increase, 10.1% annual increase) and continued to steadily increase to 115.7 in 2004 (10.7% increase, 5.2% increase per year). IOLs are classified either as monofocal, multifocal, or accommodative. Traditionally, monofocal (i.e.. fixed focusing power) IOLs are available as replacement lenses but their implantation can cause a loss of the eye's accommodative capability (which allows variable focusing). Patients thus usually require eyeglasses after surgery for reading and near vision tasks. Multifocal IOLs aim to improve near and distant vision and obviate the need for glasses. Potential disadvantages include reduced contrast sensitivity, halos around lights and glare. Accommodating IOLs are designed to move with ciliary body contraction during

  9. Impact of the Chromatin Remodeling Factor CHD1 on Gut Microbiome Composition of Drosophila melanogaster.

    Science.gov (United States)

    Sebald, Johanna; Willi, Michaela; Schoberleitner, Ines; Krogsdam, Anne; Orth-Höller, Dorothea; Trajanoski, Zlatko; Lusser, Alexandra

    2016-01-01

    The composition of the intestinal microbiota of Drosophila has been studied in some detail in recent years. Environmental, developmental and host-specific genetic factors influence microbiome composition in the fly. Our previous work has indicated that intestinal bacterial load can be affected by chromatin-targeted regulatory mechanisms. Here we studied a potential role of the conserved chromatin assembly and remodeling factor CHD1 in the shaping of the gut microbiome in Drosophila melanogaster. Using high-throughput sequencing of 16S rRNA gene amplicons, we found that Chd1 deletion mutant flies exhibit significantly reduced microbial diversity compared to rescued control strains. Specifically, although Acetobacteraceae dominated the microbiota of both Chd1 wild-type and mutant guts, Chd1 mutants were virtually monoassociated with this bacterial family, whereas in control flies other bacterial taxa constituted ~20% of the microbiome. We further show age-linked differences in microbial load and microbiota composition between Chd1 mutant and control flies. Finally, diet supplementation experiments with Lactobacillus plantarum revealed that, in contrast to wild-type flies, Chd1 mutant flies were unable to maintain higher L. plantarum titres over time. Collectively, these data provide evidence that loss of the chromatin remodeler CHD1 has a major impact on the gut microbiome of Drosophila melanogaster.

  10. Impact of the Chromatin Remodeling Factor CHD1 on Gut Microbiome Composition of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Johanna Sebald

    Full Text Available The composition of the intestinal microbiota of Drosophila has been studied in some detail in recent years. Environmental, developmental and host-specific genetic factors influence microbiome composition in the fly. Our previous work has indicated that intestinal bacterial load can be affected by chromatin-targeted regulatory mechanisms. Here we studied a potential role of the conserved chromatin assembly and remodeling factor CHD1 in the shaping of the gut microbiome in Drosophila melanogaster. Using high-throughput sequencing of 16S rRNA gene amplicons, we found that Chd1 deletion mutant flies exhibit significantly reduced microbial diversity compared to rescued control strains. Specifically, although Acetobacteraceae dominated the microbiota of both Chd1 wild-type and mutant guts, Chd1 mutants were virtually monoassociated with this bacterial family, whereas in control flies other bacterial taxa constituted ~20% of the microbiome. We further show age-linked differences in microbial load and microbiota composition between Chd1 mutant and control flies. Finally, diet supplementation experiments with Lactobacillus plantarum revealed that, in contrast to wild-type flies, Chd1 mutant flies were unable to maintain higher L. plantarum titres over time. Collectively, these data provide evidence that loss of the chromatin remodeler CHD1 has a major impact on the gut microbiome of Drosophila melanogaster.

  11. Phenotypic and genetic effects of contrasting ethanol environments on physiological and developmental traits in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Luis E Castañeda

    Full Text Available A central problem in evolutionary physiology is to understand the relationship between energy metabolism and fitness-related traits. Most attempts to do so have been based on phenotypic correlations that are not informative for the evolutionary potential of natural populations. Here, we explored the effect of contrasting ethanol environments on physiological and developmental traits, their genetic (covariances and genetic architecture in Drosophila melanogaster. Phenotypic and genetic parameters were estimated in two populations (San Fernando and Valdivia, Chile, using a half-sib family design where broods were split into ethanol-free and ethanol-supplemented conditions. Our findings show that metabolic rate, body mass and development times were sensitive (i.e., phenotypic plasticity to ethanol conditions and dependent on population origin. Significant heritabilities were found for all traits, while significant genetic correlations were only found between larval and total development time and between development time and metabolic rate for flies of the San Fernando population developed in ethanol-free conditions. Posterior analyses indicated that the G matrices differed between ethanol conditions for the San Fernando population (mainly explained by differences in genetic (covariances of developmental traits, whereas the Valdivia population exhibited similar G matrices between ethanol conditions. Our findings suggest that ethanol-free environment increases the energy available to reduce development time. Therefore, our results indicate that environmental ethanol could modify the process of energy allocation, which could have consequences on the evolutionary response of natural populations of D. melanogaster.

  12. Phenotypic and Genetic Effects of Contrasting Ethanol Environments on Physiological and Developmental Traits in Drosophila melanogaster

    Science.gov (United States)

    Castañeda, Luis E.; Nespolo, Roberto F.

    2013-01-01

    A central problem in evolutionary physiology is to understand the relationship between energy metabolism and fitness-related traits. Most attempts to do so have been based on phenotypic correlations that are not informative for the evolutionary potential of natural populations. Here, we explored the effect of contrasting ethanol environments on physiological and developmental traits, their genetic (co)variances and genetic architecture in Drosophila melanogaster. Phenotypic and genetic parameters were estimated in two populations (San Fernando and Valdivia, Chile), using a half-sib family design where broods were split into ethanol-free and ethanol-supplemented conditions. Our findings show that metabolic rate, body mass and development times were sensitive (i.e., phenotypic plasticity) to ethanol conditions and dependent on population origin. Significant heritabilities were found for all traits, while significant genetic correlations were only found between larval and total development time and between development time and metabolic rate for flies of the San Fernando population developed in ethanol-free conditions. Posterior analyses indicated that the G matrices differed between ethanol conditions for the San Fernando population (mainly explained by differences in genetic (co)variances of developmental traits), whereas the Valdivia population exhibited similar G matrices between ethanol conditions. Our findings suggest that ethanol-free environment increases the energy available to reduce development time. Therefore, our results indicate that environmental ethanol could modify the process of energy allocation, which could have consequences on the evolutionary response of natural populations of D. melanogaster. PMID:23505567

  13. Timed Knickkopf function is essential for wing cuticle formation in Drosophila melanogaster.

    Science.gov (United States)

    Li, Kaixia; Zhang, Xubo; Zuo, Ying; Liu, Weimin; Zhang, Jianzhen; Moussian, Bernard

    2017-10-01

    The insect cuticle is an extracellular matrix that consists of the polysaccharide chitin, proteins, lipids and organic molecules that are arranged in distinct horizontal layers. In Drosophila melanogaster, these layers are not formed sequentially, but, at least partially, at the same time. Timing of the underlying molecular mechanisms is conceivably crucial for cuticle formation. To study this issue, we determined the time period during which the function of Knickkopf (Knk), a key factor of chitin organization, is required for wing cuticle differentiation in D. melanogaster. Although knk is expressed throughout metamorphosis, we demonstrate that its expression 30 h prior and 48 h after pupariation is essential for correct wing cuticle formation. In other words, expression beyond this period is futile. Importantly, manipulation of Knk expression during this time causes wing bending suggesting an effect of Knk amounts on the physical properties of the wing cuticle. Manipulation of Knk expression also interferes with the structure and function of the cuticle surface. First, we show that the shape of surface nano-structures depends on the expression levels of knk. Second, we find that cuticle impermeability is compromised in wings with reduced knk expression. In summary, despite the extended supply of Knk during metamorphosis, controlled amounts of Knk are important for correct wing cuticle differentiation and function in a concise period of time. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Implications of Age-Related Changes in Anatomy for Geriatric-Focused Difficult Airways

    Directory of Open Access Journals (Sweden)

    Shih-Yi Lee

    2017-09-01

    Full Text Available The structure and function surrounding the airway change by the age, which may ultimately result in having anatomic features of difficult airways in the elderly. Hence, we reviewed the literature focusing on the age-related anatomic changes and accordingly to compare the characteristics of difficult airways. With age, teeth wear and loss, protein and collagen synthesis reduction, and bone loss and muscle atrophy results in aged face (chin protrusion, cheek retraction and drooping, jaw restriction (temporo-madibular joint disc displacement and osteoarthritis, neck and back stiffness, and kyphotic deformities (degeneration of spinal articular cartilage, intervertebral discs, and spinal osteoporosis. These age-related changes in anatomy are compatible with the predictors of a difficult airway. We hope that these age-related anatomic approaches will prospectively allow a detailed understanding of the hallmarks resulting in geriatric-focused difficult airways in the future studies.

  15. Alcohol consumption, smoking and development of visible age-related signs

    DEFF Research Database (Denmark)

    Schou, Anne L; Mølbak, Marie-Louise; Schnor, Peter

    2017-01-01

    BACKGROUND: Visible age-related signs indicate biological age, as individuals that appear old for their age are more likely to be at poor health, compared with people that appear their actual age. The aim of this study was to investigate whether alcohol and smoking are associated with four visible...... age-related signs (arcus corneae, xanthelasmata, earlobe crease and male pattern baldness). METHODS: We used information from 11 613 individuals in the Copenhagen City Heart Study (1976-2003). Alcohol intake, smoking habits and other lifestyle factors were assessed prospectively and visible age......-related signs were inspected during subsequent examinations. RESULTS: The risk of developing arcus corneae, earlobe crease and xanthelasmata increased stepwise with increased smoking as measured by pack-years. For alcohol consumption, a high intake was associated with the risk of developing arcus corneae...

  16. Puzzles in modern biology. III.Two kinds of causality in age-related disease.

    Science.gov (United States)

    Frank, Steven A

    2016-01-01

    The two primary causal dimensions of age-related disease are rate and function. Change in rate of disease development shifts the age of onset. Change in physiological function provides necessary steps in disease progression. A causal factor may alter the rate of physiological change, but that causal factor itself may have no direct physiological role. Alternatively, a causal factor may provide a necessary physiological function, but that causal factor itself may not alter the rate of disease onset. The rate-function duality provides the basis for solving puzzles of age-related disease. Causal factors of cancer illustrate the duality between rate processes of discovery, such as somatic mutation, and necessary physiological functions, such as invasive penetration across tissue barriers. Examples from cancer suggest general principles of age-related disease.

  17. Age-related variations in the microstructure of human tibial cancellous bone

    DEFF Research Database (Denmark)

    Ding, Ming; Odgaard, A; Linde, F

    2002-01-01

    A thorough understanding of the microstructure of cancellous bone is crucial for diagnosis, prophylaxis, and treatment of age-related skeletal diseases. Until now, little has been known about age-related variations in the microstructure of peripheral cancellous bone. This study quantified age......-related changes in the three-dimensional (3D) microstructure of human tibial cancellous bone. One hundred and sixty cylindrical cancellous bone specimens were produced from 40 normal proximal tibiae from 40 donors, aged 16-85 years. These specimens were micro-computed tomography (micro-CT) scanned...... increase of anisotropy and constant connectivity suggest a bone remodeling mechanism that may reorient trabecular volume orientation in aging tibial cancellous bone. The aging trabeculae align more strongly to the primary direction--parallel to the tibial longitudinal loading axis....

  18.  Age-related changes of skeletal muscles: physiology, pathology and regeneration

    Directory of Open Access Journals (Sweden)

    Aleksandra Ławniczak

    2012-06-01

    Full Text Available  This review provides a short presentation of the aging-related changes of human skeletal muscles. The aging process is associated with the loss of skeletal muscle mass (sarcopenia and strength. This results from fibre atrophy and apoptosis, decreased regeneration capacity, mitochondrial dysfunction, gradual reduction of the number of spinal cord motor neurons, and local and systemic metabolic and hormonal alterations. The latter involve age-related decrease of the expression and activity of some mitochondrial and cytoplasmic enzymes, triacylglycerols and lipofuscin accumulation inside muscle fibres, increased proteolytic activity, insulin resistance and decreased serum growth hormone and IGF-1 concentrations. Aging of the skeletal muscles is also associated with a decreased number of satellite cells and their proliferative activity. The age-related reduction of skeletal muscle mass and function may be partially prevented by dietary restriction and systematic physical exercises.

  19. Age-associated decline in mitochondrial respiration and electron transport in Drosophila melanogaster.

    Science.gov (United States)

    Ferguson, Melissa; Mockett, Robin J; Shen, Yi; Orr, William C; Sohal, Rajindar S

    2005-09-01

    The principal objective of the present study was to identify specific alterations in mitochondrial respiratory functions during the aging process. Respiration rates and the activities of electron transport chain complexes were measured at various ages in mitochondria isolated from thoraces of the fruit fly, Drosophila melanogaster, which consist primarily of flight muscles. The rates of state 3 respiration (ADP-stimulated), RCRs (respiratory control ratios) and uncoupled respiration rates decreased significantly as a function of age, using either NAD+- or FAD-linked substrates; however, there were no differences in state 4 respiration (ADP-depleted) rates. There was also a significant age-related decline in the activity of cytochrome c oxidase (complex IV), but not of the other mitochondrial oxidoreductases examined. Exposure of mitochondria isolated from young flies to low doses of KCN or NaAz (sodium azide), complex IV inhibitors, decreased cytochrome c oxidase activity and increased the production of H2O2. Collectively, these results support the hypothesis that impairment of mitochondrial respiration may be a causal factor in the aging process, and that such impairment may result from and contribute to increased H2O2 production in vivo.

  20. Paraquat exposure and Sod2 knockdown have dissimilar impacts on the Drosophila melanogaster carbonylated protein proteome

    Science.gov (United States)

    Narayanasamy, Suresh K.; Simpson, David C.; Martin, Ian; Grotewiel, Mike; Gronert, Scott

    2014-01-01

    Exposure to Paraquat and RNA interference knockdown of Mn or mitochondrial superoxide dismutase (Sod2) are known to result in significant lifespan reduction, locomotor dysfunction, and mitochondrial degeneration in Drosophila melanogaster. Both perturbations increase the flux of the progenitor ROS, superoxide, but the molecular underpinnings of the resulting phenotypes are poorly understood. Improved understanding of such processes could lead to advances in the treatment of numerous age-related disorders. Superoxide toxicity can act through protein carbonylation. Analysis of carbonylated proteins is attractive since carbonyl groups are not present in the twenty canonical amino acids and are amenable to labeling and enrichment strategies. Here, carbonylated proteins were labeled with biotin hydrazide and enriched on streptavidin beads. On-bead digestion was used to release carbonylated protein peptides, with relative abundance ratios versus controls obtained using the iTRAQ MS-based proteomics approach. Western blotting and biotin quantitation assay approaches were also investigated. By both western blotting and proteomics, Paraquat exposure, but not Sod2 knockdown, resulted in increased carbonylated protein relative abundance. For Paraquat exposure versus control, the median carbonylated protein relative abundance ratio (1.53) determined using MS-based proteomics was in good agreement with that obtained using a commercial biotin quantitation kit (1.36). PMID:25091824

  1. Visual impairment, age-related eye diseases, and cognitive function: the Singapore Malay Eye study.

    Science.gov (United States)

    Ong, Shin Yeu; Cheung, Carol Y; Li, Xiang; Lamoureux, Ecosse L; Ikram, M Kamran; Ding, Jie; Cheng, Ching Yu; Haaland, Benjamin Adam; Saw, Seang Mei; Venketasubramanian, Narayanaswamy; Chen, Christopher P L; Wong, Tien Yin

    2012-07-01

    To describe the associations of visual impairment and major age-related eye diseases with cognitive function in an older Asian population. A population-based, cross-sectional study of 1179 participants aged 60 to 80 years from the Singapore Malay Eye study was conducted. Visual acuity was measured using the logMAR vision chart. Cataract and age-related macular degeneration were graded using the Wisconsin Cataract Grading System and the Wisconsin Age-Related Maculopathy Grading System, respectively. Glaucoma was diagnosed using the International Society Geographical and Epidemiological Ophthalmology criteria. Diabetic retinopathy was graded using the modified Airlie House classification system. Cognitive dysfunction was defined as a locally validated Abbreviated Mental Test using education-based cutoff scores. After adjusting for age, sex, education level, income, and type of housing, persons with visual impairment before refractive correction (odds ratio [OR]=2.59; 95% CI, 1.89-3.56) or after refractive correction (OR=1.96; 95% CI, 1.27-3.02) and those with visual impairment due to cataract (OR=2.75; 95% CI, 1.35-5.63) were more likely to have cognitive dysfunction. Only moderate to severe diabetic retinopathy was independently associated with cognitive dysfunction (OR=5.57; 95% CI, 1.56-19.91) after controlling for concurrent age-related eye diseases. No significant independent associations were observed between cataract, age-related macular degeneration, or glaucoma and cognitive dysfunction. Older persons with visual impairment, particularly those with visual impairment due to cataract, were more likely to have cognitive dysfunction. Furthermore, among the major age-related eye diseases, only diabetic retinopathy was associated with cognitive dysfunction.

  2. Age-related differences in quality of standing balance using a composite score.

    Science.gov (United States)

    Pasma, Jantsje H; Bijlsma, Astrid Y; van der Bij, Mark D W; Arendzen, J Hans; Meskers, Carel G M; Maier, Andrea B

    2014-01-01

    Age-related differences in standing balance are not detected by testing the ability to maintain balance. Quality of standing balance might be more sensitive to detect age-related differences. To study age-related differences in quality of standing balance, center of pressure (CoP) movement was evaluated using a wide range of CoP parameters in several standing conditions in healthy young and old participants. In 35 healthy young (18-30 years) and 75 healthy old (70-80 years) participants, CoP movement was assessed in eight standing conditions on a force plate, including side-by-side, one-leg, semi-tandem and tandem stance, both with eyes open and eyes closed. Direction-specific CoP composite scores were calculated from standardized single CoP parameters (mean amplitude, amplitude variability, mean velocity, velocity variability and range) in anterior-posterior (AP) and medial-lateral (ML) direction. Linear regression analysis was used to detect age-related differences in single CoP parameters and composite scores - adjusted for gender, height and weight. Overall, single CoP parameters were higher in old compared to young participants, but no single CoP parameter consistently demonstrated the largest effect size for all standing conditions. Age-related differences were demonstrated for CoP composite scores in AP direction (tandem eyes open; semi-tandem eyes closed; p CoP composite scores in ML direction were consistently higher for all standing conditions in old compared to young participants (p CoP composite scores in ML direction were the most consistent parameters to detect age-related differences in quality of standing balance in healthy participants and might be of clinical value to detect subtle changes in quality of standing balance. © 2014 S. Karger AG, Basel

  3. Age-related spontaneous lumbar intervertebral disc degeneration in a mouse model.

    Science.gov (United States)

    Ohnishi, Takashi; Sudo, Hideki; Tsujimoto, Takeru; Iwasaki, Norimasa

    2018-01-01

    The pathogenesis of intervertebral disc degeneration is unclear, but it is a major cause of several spinal diseases. Animal models have historically provided an appropriate benchmark for understanding the human spine. However, there is little information about when intervertebral disc degeneration begins in the mouse or regarding the relationship between magnetic resonance imaging and histological findings. The aim for this study was to obtain information about age-related spontaneous intervertebral disc degeneration in the mouse lumbar spine using magnetic resonance imaging and a histological score regarding when the intervertebral disc degeneration started and how rapidly it progressed, as well as how our histological score detected the degeneration. The magnetic resonance imaging index yielded a moderate correlation with our Age-related model score. The Pfirrmann grade and magnetic resonance imaging index had moderate correlations with age. However, our Age-related model score had a high correlation with age. Intervertebral disc level was not a significant variable for the severity of disc degeneration. Both Pfirrmann grade and the Age-related model score were higher in the ≥14-month-old group than in the 6-month-old group. The present results indicated that mild but significant intervertebral disc degeneration occurred in 14-month-old mice, and the degree of degeneration progressed slowly, reaching a moderate to severe condition for 22-month-old mice. At least a 14-month follow-up is mandatory for evaluating spontaneous age-related mouse intervertebral disc degeneration. The histological classification score can precisely detect the gradual progression of age-related spontaneous intervertebral disc degeneration in the mouse lumbar spine, and is appropriate for evaluating it. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:224-232, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  4. Over the hill at 24: persistent age-related cognitive-motor decline in reaction times in an ecologically valid video game task begins in early adulthood.

    Directory of Open Access Journals (Sweden)

    Joseph J Thompson

    Full Text Available Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load.

  5. Over the hill at 24: persistent age-related cognitive-motor decline in reaction times in an ecologically valid video game task begins in early adulthood.

    Science.gov (United States)

    Thompson, Joseph J; Blair, Mark R; Henrey, Andrew J

    2014-01-01

    Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load.

  6. Over the Hill at 24: Persistent Age-Related Cognitive-Motor Decline in Reaction Times in an Ecologically Valid Video Game Task Begins in Early Adulthood

    Science.gov (United States)

    Thompson, Joseph J.; Blair, Mark R.; Henrey, Andrew J.

    2014-01-01

    Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load. PMID:24718593

  7. Risk factors associated with age-related nuclear and cortical cataract : a case-control study in the Age-Related Eye Disease Study, AREDS Report No. 5.

    Science.gov (United States)

    2001-08-01

    To investigate possible risk factors for age-related nuclear and cortical cataracts in participants in the Age-Related Eye Disease Study (AREDS). Case-control study. Of the 4757 persons enrolled in AREDS, 4477 age 60 to 80 years are included in the study. Slit-lamp lens photographs were used to classify participants into one of three nuclear opacity groups (moderate nuclear, mild nuclear, and controls), ignoring cortical opacities. Retroillumination lens photographs were used to classify participants into one of three cortical opacity groups (moderate cortical, mild cortical, and controls), ignoring nuclear opacities. Persons with moderate nuclear opacities were more likely to be female, nonwhite, and smokers and to have large drusen. Moderate nuclear opacities were less common in persons with higher educational status, a history of diabetes, and among those taking nonsteroidal antiinflammatory drugs. Moderate cortical opacities were associated with dark iris color, large drusen, weight change, and, at a borderline level of significance, higher levels of sunlight exposure and use of thyroid hormones. Moderate cortical opacities were less common in persons with higher educational status. Consistent findings have now been reported across many studies for gender, educational status, sunlight exposure, and smoking. Our findings that use of nonsteroidal antiinflammatory drugs is inversely associated with nuclear cataract and that dark iris color and use of thyroid hormones may increase cortical cataract risk are less well substantiated and require further investigation.

  8. Improved word recognition for observers with age-related maculopathies using compensation filters

    Science.gov (United States)

    Lawton, Teri B.

    1988-01-01

    A method for improving word recognition for people with age-related maculopathies, which cause a loss of central vision, is discussed. It is found that the use of individualized compensation filters based on an person's normalized contrast sensitivity function can improve word recognition for people with age-related maculopathies. It is shown that 27-70 pct more magnification is needed for unfiltered words compared to filtered words. The improvement in word recognition is positively correlated with the severity of vision loss.

  9. Aging of marrow stromal (skeletal) stem cells and their contribution to age-related bone loss

    DEFF Research Database (Denmark)

    Bellantuono, Ilaria; Aldahmash, Abdullah; Kassem, Moustapha

    2009-01-01

    Marrow stromal cells (MSC) are thought to be stem cells with osteogenic potential and therefore responsible for the repair and maintenance of the skeleton. Age related bone loss is one of the most prevalent diseases in the elder population. It is controversial whether MSC undergo a process of aging...... in vivo, leading to decreased ability to form and maintain bone homeostasis with age. In this review we summarize evidence of MSC involvement in age related bone loss and suggest new emerging targets for intervention....

  10. Blueberry-enriched diet ameliorates age-related declines in NMDA receptor-dependent LTP

    OpenAIRE

    Coultrap, Steven J.; Bickford, Paula C.; Browning, Michael D.

    2008-01-01

    NMDA receptor-dependent long-term potentiation (LTP) in the hippocampus is widely accepted as a cellular substrate for memory formation. Age-related declines in the expression of both NMDAR-dependent LTP and NMDAR subunit proteins in the CA1 region of the hippocampus have been well characterized and likely underlie age-related memory impairment. In the current study, we examined NMDAR-dependent LTP in young Fischer 344 rats (4?months old) and aged rats (24?months old) given either a control d...

  11. The Potential of Chitosan and Its Derivatives in Prevention and Treatment of Age-Related Diseases

    Science.gov (United States)

    Kerch, Garry

    2015-01-01

    Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed. PMID:25871293

  12. Age-related change in Wechsler IQ norms after adjustment for the Flynn effect: estimates from three computational models.

    Science.gov (United States)

    Agbayani, Kristina A; Hiscock, Merrill

    2013-01-01

    A previous study found that the Flynn effect accounts for 85% of the normative difference between 20- and 70-year-olds on subtests of the Wechsler intelligence tests. Adjusting scores for the Flynn effect substantially reduces normative age-group differences, but the appropriate amount of adjustment is uncertain. The present study replicates previous findings and employs two other methods of adjusting for the Flynn effect. Averaged across models, results indicate that the Flynn effect accounts for 76% of normative age-group differences on Wechsler IQ subtests. Flynn-effect adjustment reduces the normative age-related decline in IQ from 4.3 to 1.1 IQ points per decade.

  13. European survey on the opinion and use of micronutrition in age-related macular degeneration: 10 years on from the Age-Related Eye Disease Study

    Directory of Open Access Journals (Sweden)

    Aslam T

    2014-10-01

    Full Text Available Tariq Aslam,1 Cécile Delcourt,2 Frank Holz,3 Alfredo García-Layana,4 Anita Leys,5 Rufino M Silva,6 Eric Souied7 1Manchester Royal Eye Hospital, Manchester, UK; 2University of Bordeaux, Bordeaux, France; 3University of Bonn, Bonn, Germany; 4Clínica Universidad de Navarra, Pamplona, Spain; 5University Hospitals, Leuven, Belgium; 6University of Coimbra, Coimbra, Portugal; 7Université Paris Est Créteil, Créteil, FrancePurpose: To evaluate ophthalmologists’ opinion of, and use of, micronutritional dietary supplements 10 years after publication of the first Age-Related Eye Disease Study (AREDS study.Methods: Participation was solicited from 4,000 European ophthalmologists. Responding physicians were screened, and those treating at least 40 patients with age-related macular degeneration (AMD per month and prescribing nutrition supplements at least 4 times per month were admitted and completed a 40-item questionnaire.Results: The surveyed sample included 112 general ophthalmologists and 104 retinal specialists. Most nutritional supplements (46% were initiated when early/intermediate AMD was confirmed, although 18% were initiated on confirmation of neovascular AMD. Clinical studies were well known: 90% were aware of AREDS, with 88% aware of AREDS1 and 36% aware of the, as-yet-unpublished, AREDS2 studies. Respondents considered lutein, zeaxanthin, zinc, omega-3, and vitamins to be the most important components of nutritional supplements, with the results of AREDS2 already having been taken into consideration by many. Ophthalmologists anticipate more scientific studies as well as improved product quality but identify cost as a barrier to wider uptake.Conclusion: Micronutrition is now part of the routine management of AMD for many ophthalmologists. Ophthalmologists choosing to use nutritional supplements are well-informed regarding current scientific studies. Keywords: age-related macular degeneration, micronutrition, nutritional

  14. Wandering stars: age-related habitat use and dispersal of Javan Hawk-eagles (Spizaetus bartelsi)

    NARCIS (Netherlands)

    Nijman, V.; Balen, van S.

    2003-01-01

    Natal dispersal and philopatry have rarely been studied in tropical forest raptors. Especially with respect to endangered species with fragmented distributions more knowledge of dispersal and age-related habitat preferences is needed for proper management. We conducted an island-wide study on

  15. Visualization of dietary patterns and their associations with age-related macular degeneration

    Science.gov (United States)

    PURPOSE: We aimed to visualize the relationship of predominant dietary patterns and their associations with AMD. METHODS: A total of 8103 eyes from 4088 participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into three groups: control (n=2739), early AMD (n=4599), and adv...

  16. Shared and Unique Genetic and Environmental Influences on Aging-Related Changes in Multiple Cognitive Abilities

    Science.gov (United States)

    Tucker-Drob, Elliot M.; Reynolds, Chandra A.; Finkel, Deborah; Pedersen, Nancy L.

    2014-01-01

    Aging-related declines occur in many different domains of cognitive function during middle and late adulthood. However, whether a global dimension underlies individual differences in changes in different domains of cognition and whether global genetic influences on cognitive changes exist is less clear. We addressed these issues by applying…

  17. Harmonizing the classification of age-related macular degeneration in the three-continent AMD consortium

    NARCIS (Netherlands)

    Klein, Ronald; Meuer, Stacy M; Myers, Chelsea E; Buitendijk, Gabriëlle H S; Rochtchina, Elena; Choudhury, Farzana; de Jong, Paulus T V M; McKean-Cowdin, Roberta; Iyengar, Sudha K; Gao, Xiaoyi; Lee, Kristine E; Vingerling, Johannes R; Mitchell, Paul; Klaver, Caroline C W; Wang, Jie Jin; Klein, Barbara E K

    PURPOSE: To describe methods to harmonize the classification of age-related macular degeneration (AMD) phenotypes across four population-based cohort studies: the Beaver Dam Eye Study (BDES), the Blue Mountains Eye Study (BMES), the Los Angeles Latino Eye Study (LALES), and the Rotterdam Study (RS).

  18. Near-infrared reflectance imaging of neovascular age-related macular degeneration.

    NARCIS (Netherlands)

    Theelen, T.; Berendschot, T.T.; Hoyng, C.B.; Boon, C.J.F.; Klevering, B.J.

    2009-01-01

    PURPOSE: To evaluate various types of neovascular age-related macular degeneration (AMD) by near-infrared fundus reflectance (NIR) as compared to fundus fluorescein angiography (FFA) and to test NIR for assessment of leakage due to choroidal neovascularization (CNV). PATIENTS AND METHODS:

  19. Age-related changes in the sleep pattern of male adult rats

    NARCIS (Netherlands)

    van Gool, W. A.; Mirmiran, M.

    1983-01-01

    In order to study whether or not the age-related changes in the sleep pattern observed in humans also occur in rats, young adult (4 months) and old (22 months) male Wistar rats were implanted with EEG and EMG electrodes for 24 h on-line registration by means of an automatic sleep-classifier. During

  20. Age Related Pattern And Outcome Of Head Injury In Indigenous Africa

    African Journals Online (AJOL)

    Background: Most studies of patients with head injury managed outside of indigenous Africa have shown poorer outcome with increasing age, but data on this subject is scanty in this part of the world. Aim: To determine age related pattern and outcome of head injury in an indigenous African setting. Methods: A retrospective ...

  1. Psychosocial Intervention for Age-Related Macular Degeneration: A Pilot Project

    Science.gov (United States)

    Wahl, Hans-Werner; Kammerer, Annette; Holz, Frank; Miller, Daniel; Becker, Stefanie; Kaspar, Roman; Himmelsbach, Ines

    2006-01-01

    This study evaluated an emotion-focused and a problem-focused intervention designed for patients with age-related macular degeneration. It found a limited decrease in depression in the emotion-focused group and an increase in active problem orientation and in adaptation to vision loss in the problem-focused group.

  2. Masking Period Patterns & Forward Masking for Speech-Shaped Noise: Age-related effects

    Science.gov (United States)

    Grose, John H.; Menezes, Denise C.; Porter, Heather L.; Griz, Silvana

    2015-01-01

    Objective The purpose of this study was to assess age-related changes in temporal resolution in listeners with relatively normal audiograms. The hypothesis was that increased susceptibility to non-simultaneous masking contributes to the hearing difficulties experienced by older listeners in complex fluctuating backgrounds. Design Participants included younger (n = 11), middle-aged (n = 12), and older (n = 11) listeners with relatively normal audiograms. The first phase of the study measured masking period patterns for speech-shaped noise maskers and signals. From these data, temporal window shapes were derived. The second phase measured forward-masking functions, and assessed how well the temporal window fits accounted for these data. Results The masking period patterns demonstrated increased susceptibility to backward masking in the older listeners, compatible with a more symmetric temporal window in this group. The forward-masking functions exhibited an age-related decline in recovery to baseline thresholds, and there was also an increase in the variability of the temporal window fits to these data. Conclusions This study demonstrated an age-related increase in susceptibility to non-simultaneous masking, supporting the hypothesis that exacerbated non-simultaneous masking contributes to age-related difficulties understanding speech in fluctuating noise. Further support for this hypothesis comes from limited speech-in-noise data suggesting an association between susceptibility to forward masking and speech understanding in modulated noise. PMID:26230495

  3. Masking Period Patterns and Forward Masking for Speech-Shaped Noise: Age-Related Effects.

    Science.gov (United States)

    Grose, John H; Menezes, Denise C; Porter, Heather L; Griz, Silvana

    2016-01-01

    The purpose of this study was to assess age-related changes in temporal resolution in listeners with relatively normal audiograms. The hypothesis was that increased susceptibility to nonsimultaneous masking contributes to the hearing difficulties experienced by older listeners in complex fluctuating backgrounds. Participants included younger (n = 11), middle-age (n = 12), and older (n = 11) listeners with relatively normal audiograms. The first phase of the study measured masking period patterns for speech-shaped noise maskers and signals. From these data, temporal window shapes were derived. The second phase measured forward-masking functions and assessed how well the temporal window fits accounted for these data. The masking period patterns demonstrated increased susceptibility to backward masking in the older listeners, compatible with a more symmetric temporal window in this group. The forward-masking functions exhibited an age-related decline in recovery to baseline thresholds, and there was also an increase in the variability of the temporal window fits to these data. This study demonstrated an age-related increase in susceptibility to nonsimultaneous masking, supporting the hypothesis that exacerbated nonsimultaneous masking contributes to age-related difficulties understanding speech in fluctuating noise. Further support for this hypothesis comes from limited speech-in-noise data, suggesting an association between susceptibility to forward masking and speech understanding in modulated noise.

  4. Obesity and Age-Related Changes in Markers of Oxidative Stress and Inflammation Across Four Generations

    NARCIS (Netherlands)

    Hulsegge, Gerben; Herber-Gast, Gerrie-Cor M; Spijkerman, Annemieke M W; Susan, H; Picavet, J; van der Schouw, Yvonne T; Bakker, Stephan J L; Gansevoort, Ron T; Dollé, Martijn E T; Smit, Henriette A; Monique Verschuren, W M

    ObjectiveThe prevalence of obesity increases with age and is higher in each younger generation (unfavorable generation shift). This may influence patterns of oxidative stress and inflammation. Age-related changes and generation shifts in markers of oxidative stress and inflammation were

  5. Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages

    NARCIS (Netherlands)

    Schick, T.; Altay, L.; Viehweger, E.; Hoyng, C.B.; Hollander, A.I. den; Felsch, M.; Fauser, S.

    2016-01-01

    BACKGROUND: Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic

  6. Heritability of Anxious-Depressive and Withdrawn Behavior: Age-Related Changes during Adolescence

    Science.gov (United States)

    Lamb, Diane J.; Middeldorp, Christel M.; van Beijsterveldt, Catarina E. M.; Bartels, Meike; van der Aa, Niels; Polderman, Tinca J. C.; Boomsma, Dorret I.

    2010-01-01

    Objective: To explain the differential course of anxiety and depression in individuals from childhood to adulthood by examining age-related changes in the genetic and environmental etiology of anxious and depressive symptoms. Method: A sample of 1470, 1839, and 2023 Dutch twins aged 12, 14, and 16 years reported on symptoms of anxious depression…

  7. Ability of university-level education to prevent age-related decline in emotional intelligence

    Science.gov (United States)

    Cabello, Rosario; Navarro Bravo, Beatriz; Latorre, José Miguel; Fernández-Berrocal, Pablo

    2014-01-01

    Numerous studies have suggested that educational history, as a proxy measure of active cognitive reserve, protects against age-related cognitive decline and risk of dementia. Whether educational history also protects against age-related decline in emotional intelligence (EI) is unclear. The present study examined ability EI in 310 healthy adults ranging in age from 18 to 76 years using the Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT). We found that older people had lower scores than younger people for total EI and for the EI branches of perceiving, facilitating, and understanding emotions, whereas age was not associated with the EI branch of managing emotions. We also found that educational history protects against this age-related EI decline by mediating the relationship between age and EI. In particular, the EI scores of older adults with a university education were higher than those of older adults with primary or secondary education, and similar to those of younger adults of any education level. These findings suggest that the cognitive reserve hypothesis, which states that individual differences in cognitive processes as a function of lifetime intellectual activities explain differential susceptibility to functional impairment in the presence of age-related changes and brain pathology, applies also to EI, and that education can help preserve cognitive-emotional structures during aging. PMID:24653697

  8. HISTORY OF SUNLIGHT EXPOSURE IS A RISK FACTOR FOR AGE-RELATED MACULAR DEGENERATION

    NARCIS (Netherlands)

    Schick, T.; Ersoy, L.; Lechanteur, Y.T.; Saksens, N.T.; Hoyng, C.B.; Hollander, A.I. den; Kirchhof, B.; Fauser, S.

    2016-01-01

    PURPOSE: To evaluate effects of current and past sunlight exposure and iris color on early and late age-related macular degeneration (AMD). METHODS: Of 3,701 individuals from the EUGENDA database, 752 (20.3%) showed early AMD, 1,179 (31.9%) late AMD, and 1,770 (47.8%) were controls. Information

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

    Indian Academy of Sciences (India)

    We studied the structures of the cerebellar cortex of young adult and old cats for age-related changes, which were statistically analysed. Nissl staining was used to visualize the cortical neurons. The immunohistochemical method was used to display glial fibrillary acidic protein (GFAP)-immunoreactive (IR) astrocytes and ...

  10. The potential effects of meditation on age-related cognitive decline: a systematic review.

    Science.gov (United States)

    Gard, Tim; Hölzel, Britta K; Lazar, Sara W

    2014-01-01

    With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline. © 2013 New York Academy of Sciences.

  11. Multiple gait parameters derived from iPod accelerometry predict age-related gait changes

    NARCIS (Netherlands)

    Kosse, Nienke; Vuillerme, Nicolas; Hortobagyi, Tibor; Lamoth, Claude

    Introduction Normative data of how natural aging affects gait can serve as a frame of reference for changes in gait dynamics due to pathologies. Therefore, the present study aims (1) to identify gait variables sensitive to age-related changes in gait over the adult life span using the iPod and (2)

  12. Assessing Age-Related Etiologic Heterogeneity in the Onset of Islet Autoimmunity

    Directory of Open Access Journals (Sweden)

    Brittni N. Frederiksen

    2015-01-01

    Full Text Available Type 1 diabetes (T1D, a chronic autoimmune disease, is often preceded by a preclinical phase of islet autoimmunity (IA where the insulin-producing beta cells of the pancreas are destroyed and circulating autoantibodies can be detected. The goal of this study was to demonstrate methods for identifying exposures that differentially influence the disease process at certain ages by assessing age-related heterogeneity. The Diabetes Autoimmunity Study in the Young (DAISY has followed 2,547 children at increased genetic risk for T1D from birth since 1993 in Denver, Colorado, 188 of whom developed IA. Using the DAISY population, we evaluated putative determinants of IA, including non-Hispanic white (NHW ethnicity, maternal age at birth, and erythrocyte membrane n-3 fatty acid (FA levels, for age-related heterogeneity. A supremum test, weighted Schoenfeld residuals, and restricted cubic splines were used to assess nonproportional hazards, that is, an age-related association of the exposure with IA risk. NHW ethnicity, maternal age, and erythrocyte membrane n-3 FA levels demonstrated a significant age-related association with IA risk. Assessing heterogeneity in disease etiology enables researchers to identify associations that may lead to better understanding of complex chronic diseases.

  13. Amniotic epithelial cells: a new tool to combat aging and age-related diseases?

    Directory of Open Access Journals (Sweden)

    Clara Di Germanio

    2016-11-01

    Full Text Available The number of elderly people is growing at an unprecedented rate and this increase of the aging population is expected to have a direct impact on the incidence of age-related diseases and healthcare-associated costs. Thus, it is imperative that new tools are developed to fight and slow age-related diseases. Regenerative medicine is a promising strategy for the maintenance of health and function late in life; however, stem cell-based therapies face several challenges including rejection and tumor transformation. As an alternative, the placenta offers an extraordinary source of fetal stem cells, including the amniotic epithelial cells (AECs, which retain some of the characteristics of embryonic stem cells, but show low immunogenicity, together with immunomodulatory and anti-inflammatory activities. Because of these characteristics, AECs have been widely utilized in regenerative medicine. This perspective highlights different mechanisms triggered by transplanted AECs that could be potentially useful for anti-aging therapies, which include: Graft and differentiation for tissue regeneration in age-related settings, anti-inflammatory behavior to combat inflammaging, anti-tumor activity, direct lifespan and healthspan extension properties, and possibly rejuvenation in a manner reminiscent of heterochronic parabiosis.Here, we critically discuss benefits and limitation of AECs-based therapies in age-related diseases.

  14. Amniotic Epithelial Cells: A New Tool to Combat Aging and Age-Related Diseases?

    Science.gov (United States)

    Di Germanio, Clara; Bernier, Michel; de Cabo, Rafael; Barboni, Barbara

    2016-01-01

    The number of elderly people is growing at an unprecedented rate and this increase of the aging population is expected to have a direct impact on the incidence of age-related diseases and healthcare-associated costs. Thus, it is imperative that new tools are developed to fight and slow age-related diseases. Regenerative medicine is a promising strategy for the maintenance of health and function late in life; however, stem cell-based therapies face several challenges including rejection and tumor transformation. As an alternative, the placenta offers an extraordinary source of fetal stem cells, including the amniotic epithelial cells (AECs), which retain some of the characteristics of embryonic stem cells, but show low immunogenicity, together with immunomodulatory and anti-inflammatory activities. Because of these characteristics, AECs have been widely utilized in regenerative medicine. This perspective highlights different mechanisms triggered by transplanted AECs that could be potentially useful for anti-aging therapies, which include: Graft and differentiation for tissue regeneration in age-related settings, anti-inflammatory behavior to combat "inflammaging," anti-tumor activity, direct lifespan and healthspan extension properties, and possibly rejuvenation in a manner reminiscent of heterochronic parabiosis. Here, we critically discuss benefits and limitation of AECs-based therapies in age-related diseases.

  15. Mediterranean Diet Score and Its Association with Age-Related Macular Degeneration : The European Eye Study

    NARCIS (Netherlands)

    Hogg, Ruth E; Woodside, Jayne V; McGrath, Alanna; Young, Ian S; Vioque, Jesus L; Chakravarthy, Usha; de Jong, Paulus T; Rahu, Mati; Seland, Johan; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Fletcher, Astrid E

    2017-01-01

    PURPOSE: To examine associations between adherence to a Mediterranean diet and prevalence of age-related macular degeneration (AMD) in countries ranging from Southern to Northern Europe. DESIGN: Cross-sectional, population-based epidemiologic study. PARTICIPANTS: Of 5060 randomly sampled people aged

  16. Tryptophan metabolism : entering the field of aging and age-related pathologies

    NARCIS (Netherlands)

    van der Goot, Annemieke T.; Nollen, Ellen A. A.

    Aging is an important risk factor for many debilitating diseases, including cancer and neurodegeneration. In model organisms, interfering with metabolic signaling pathways, including the insulin/insulin-like growth factor (IGF) 1 (IIS) and TOR pathways, can protect against age-related pathologies

  17. Senescent cells: a novel therapeutic target for aging and age-related diseases

    NARCIS (Netherlands)

    Naylor, R.M.; Baker, D.J.; Deursen, J.M.A. van

    2013-01-01

    Aging is the main risk factor for most chronic diseases, disabilities, and declining health. It has been proposed that senescent cells--damaged cells that have lost the ability to divide--drive the deterioration that underlies aging and age-related diseases. However, definitive evidence for this

  18. Vitamin K’s role in age-related bone loss: A critical review

    Science.gov (United States)

    The protective role of vitamin K in age-related bone loss continues to be controversial. The results of observational analyses are inconsistent with respect to associations between vitamin K status and bone, which arguably may be related to the limitations of observational study designs and analyt...

  19. TYPE 2 (SUBRETINAL) NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH PURE RETICULAR PSEUDODRUSEN PHENOTYPE.

    Science.gov (United States)

    Naysan, Jonathan; Jung, Jesse J; Dansingani, Kunal K; Balaratnasingam, Chandrakumar; Freund, K Bailey

    2016-03-01

    To report the association of pure type 2 neovascularization (NV) in age-related macular degeneration occurring almost exclusively in patients with reticular pseudodrusen. An observational retrospective cohort study of all eyes receiving antivascular endothelial growth factor therapy for newly diagnosed neovascular age-related macular degeneration by a single practitioner over a 6-year period. Only patients with treatment-naive, pure type 2 NV who also had either pre-neovascular imaging of the study eye or imaging of a nonneovascular fellow eye available to determine baseline characteristics including drusen type and choroidal thickness were incuded. Of 694 patients treated for neovascular age-related macular degeneration, only 8 met the inclusion criteria with pure type 2 NV. Of these, 7 (88%) had exclusively reticular pseudodrusen (5 in the nonneovascular fellow eye, 2 in the study eye before developing NV). Six (75%) patients in the affected neovascular eye and 6 (75%) in the fellow nonneovascular eye had choroidal thickness age-related macular degeneration, occurring almost exclusively in patients with reticular pseudodrusen and thin choroids.

  20. Evaluation of circulating miRNAs in wet age-related macular degeneration.

    Science.gov (United States)

    Ertekin, Sevda; Yıldırım, Ozlem; Dinç, Erdem; Ayaz, Lokman; Fidancı, Senay Balcı; Tamer, Lülüfer

    2014-01-01

    In the present study, we aimed to investigate the changes in plasma miRNA in patients with wet age-related macular degeneration. The expression profiles of 384 miRNAs in plasma from 33 patients (22 male, 11 female) who were diagnosed with wet age-related macular degeneration with fundus examination, fundus fluorescein angiography, and optical coherence tomography and 31 controls (17 male, 14 female) were evaluated using high-throughput quantitative real-time PCR. Our results demonstrated that the expression level of five miRNAs (miR-17-5p, miR-20a-5p, miR-24-3p, miR-106a-5p, and miR-223-3p) was significantly upregulated in patients with age-related macular degeneration when compared to the control group (page-related macular degeneration. These molecules may have an important therapeutic target in patients who are unresponsive to antivascular endothelial growth factor therapy. However, further studies must be conducted for possible effects of miRNAs in vascular disorders of eye such as age-related macular degeneration.

  1. Fruits, Nuts, and Brain Aging: Nutritional Interventions Targeting Age-Related Neuronal and Behavioral Deficits

    Science.gov (United States)

    By the year 2050, 30% of the total population of the US will be over 65 years of age. As the aged population expands, the economic burden of care and treatment of those with age-related health disorders also increases, necessitating the immediate implementation of therapeutics to prevent or even rev...

  2. Role of growth factors and the wound healing response in age-related macular degeneration

    NARCIS (Netherlands)

    Schlingemann, Reinier O.

    2004-01-01

    Growth factors (GF) are important in several stages of the pathogenesis of age-related macular disease (AMD). In choroidal neovascularization (CNV) in exudative AMD, the GF involved are similar to those involved in wound healing of the skin. Like granulation tissue of skin, CNV is characterized by

  3. Age-related deficits in the mnemonic similarity task for objects and scenes.

    Science.gov (United States)

    Stark, Shauna M; Stark, Craig E L

    2017-08-30

    Using the Mnemonic Similarity Task (MST), we have demonstrated an age-related impairment in lure discrimination, or the ability to recognize an item as distinct from one that was similar, but not identical to one viewed earlier. A growing body of evidence links these behavioral changes to age-related alterations in the hippocampus. In this study, we sought to evaluate a novel version of this task, utilizing scenes that might emphasize the role of the hippocampus in contextual and spatial processing. In addition, we investigated whether, by utilizing two stimulus classes (scenes and objects), we could also interrogate the roles of the PRC and PHC in aging. Thus, we evaluated differential contributions to these tasks by relating performance on objects versus scenes to volumes of the hippocampus and surrounding medial temporal lobe structures. We found that while there was an age-related impairment on lure discrimination performance for both objects and scenes, relationships to brain volumes and other measure of memory performance were stronger when using objects. In particular, lure discrimination performance for objects showed a positive relationship with the volume of the hippocampus, specifically the combined dentate gyrus (DG) and CA3 subfields, and the subiculum. We conclude that though using scenes was effective in detecting age-related lure discrimination impairments, it does not provide as strong a brain-behavior relationship as using objects. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Age-related changes to the neural correlates of working memory which emerge after midlife

    Science.gov (United States)

    Macpherson, Helen N.; White, David J.; Ellis, Kathryn A.; Stough, Con; Camfield, David; Silberstein, Richard; Pipingas, Andrew

    2014-01-01

    Previous research has indicated that the neural processes which underlie working memory change with age. Both age-related increases and decreases to cortical activity have been reported. This study investigated which stages of working memory are most vulnerable to age-related changes after midlife. To do this we examined age-differences in the 13 Hz steady state visually evoked potential (SSVEP) associated with a spatial working memory delayed response task. Participants were 130 healthy adults separated into a midlife (40–60 years) and an older group (61–82 years). Relative to the midlife group, older adults demonstrated greater bilateral frontal activity during encoding and this pattern of activity was related to better working memory performance. In contrast, evidence of age-related under activation was identified over left frontal regions during retrieval. Findings from this study suggest that after midlife, under-activation of frontal regions during retrieval contributes to age-related decline in working memory performance. PMID:24795625

  5. Use of a robotic device to measure age-related decline in finger proprioception.

    Science.gov (United States)

    Ingemanson, Morgan L; Rowe, Justin B; Chan, Vicky; Wolbrecht, Eric T; Cramer, Steven C; Reinkensmeyer, David J

    2016-01-01

    Age-related changes in proprioception are known to affect postural stability, yet the extent to which such changes affect the finger joints is poorly understood despite the importance of finger proprioception in the control of skilled hand movement. We quantified age-related changes in finger proprioception in 37 healthy young, middle-aged, and older adults using two robot-based tasks wherein participants' index and middle fingers were moved by an exoskeletal robot. The first task assessed finger position sense by asking participants to indicate when their index and middle fingers were directly overlapped during a passive crisscross movement; the second task assessed finger movement detection by asking participants to indicate the onset of passive finger movement. When these tasks were completed without vision, finger position sense errors were 48 % larger in older adults compared to young participants (p proprioceptive reaction time was 78 % longer in older adults compared to young adults (p proprioception, these age-related differences were no longer apparent. No difference between dominant and non-dominant hand performance was found for either proprioception task. These findings demonstrate that finger proprioception is impaired in older adults, and visual feedback can be used to compensate for this deficit. The findings also support the feasibility and utility of the FINGER robot as a sensitive tool for detecting age-related decline in proprioception.

  6. Macular pigment and melanin in age-related maculopathy in a general population

    NARCIS (Netherlands)

    Berendschot, Tos T. J. M.; Willemse-Assink, Jacqueline J. M.; Bastiaanse, Mieke; de Jong, Paulus T. V. M.; van Norren, Dirk

    2002-01-01

    It has been suggested that macular pigment (MP) and melanin may protect against age-related maculopathy (ARM). To check this, MP and melanin optical density were measured in a random population-based sample of subjects 55 years of age or older. Spectral fundus reflectance of the fovea was measured

  7. A novel radial water tread maze tracks age-related cognitive decline in mice

    Directory of Open Access Journals (Sweden)

    Christina Pettan-Brewer

    2013-10-01

    Full Text Available There is currently no treatment and cure for age-related dementia and cognitive impairment in humans. Mice suffer from age-related cognitive decline just as people do, but assessment is challenging because of cumbersome and at times stressful performance tasks. We developed a novel radial water tread (RWT maze and tested male C57BL/6 (B6 and C57BL/6 x Balb/c F1 (CB6F1 mice at ages 4, 12, 20, and 28 months. B6 mice showed a consistent learning experience and memory retention that gradually decreased with age. CB6F1 mice showed a moderate learning experience in the 4 and 12 month groups, which was not evident in the 20 and 28 month groups. In conclusion, CB6F1 mice showed more severe age-related cognitive impairment compared to B6 mice and might be a suitable model for intervention studies. In addition, the RWT maze has a number of operational advantages compared to currently accepted tasks and can be used to assess age-related cognition impairment in B6 and CB6F1 mice as early as 12 months of age.

  8. GRM7 variants confer susceptibility to age-related hearing impairment.

    NARCIS (Netherlands)

    Friedman, R.A.; Laer, L. van; Huentelman, M.J.; Sheth, S.S.; Eyken, E. van; Corneveaux, J.J.; Tembe, W.D.; Halperin, R.F.; Thorburn, A.Q.; Thys, S.; Bonneux, S.; Fransen, E.; Huyghe, J.; Pyykko, I.; Cremers, C.W.R.J.; Kremer, H.; Dhooge, I.J.; Stephens, D.; Orzan, E.; Pfister, M.; Bille, M.; Parving, A.; Sorri, M.; Heyning, P. van de; Makmura, L.; Ohmen, J.D.; Linthicum Jr, F.H.; Fayad, J.N.; Pearson, J.V.; Craig, D.W.; Stephan, D.A.; Camp, G. van

    2009-01-01

    Age-related hearing impairment (ARHI), or presbycusis, is the most prevalent sensory impairment in the elderly. ARHI is a complex disease caused by an interaction between environmental and genetic factors. Here we describe the results of the first whole genome association study for ARHI. The study

  9. Aging-related concerns and body image: possible future implications for eating disorders.

    Science.gov (United States)

    Gupta, M A; Schork, N J

    1993-12-01

    We observed a direct correlation between aging-related concerns about the appearance and Drive for Thinness (Eating Disorders Inventory [EDI]), among males (n = 71) (Pearson r = .36, p youthful looks and both Drive for Thinness (EDI) (Pearson r = .44, p important future implications in the development of eating disorders, as our society continues to place an inordinate value on youthful looks.

  10. Prediction and characterization of human ageing-related proteins by using machine learning.

    Science.gov (United States)

    Kerepesi, Csaba; Daróczy, Bálint; Sturm, Ádám; Vellai, Tibor; Benczúr, András

    2018-03-06

    Ageing has a huge impact on human health and economy, but its molecular basis - regulation and mechanism - is still poorly understood. By today, more than three hundred genes (almost all of them function as protein-coding genes) have been related to human ageing. Although individual ageing-related genes or some small subsets of these genes have been intensively studied, their analysis as a whole has been highly limited. To fill this gap, for each human protein we extracted 21000 protein features from various databases, and using these data as an input to state-of-the-art machine learning methods, we classified human proteins as ageing-related or non-ageing-related. We found a simple classification model based on only 36 protein features, such as the "number of ageing-related interaction partners", "response to oxidative stress", "damaged DNA binding", "rhythmic process" and "extracellular region". Predicted values of the model quantify the relevance of a given protein in the regulation or mechanisms of the human ageing process. Furthermore, we identified new candidate proteins having strong computational evidence of their important role in ageing. Some of them, like Cytochrome b-245 light chain (CY24A) and Endoribonuclease ZC3H12A (ZC12A) have no previous ageing-associated annotations.

  11. Alcohol consumption, smoking and development of visible age-related signs: a prospective cohort study.

    Science.gov (United States)

    Schou, Anne L; Mølbak, Marie-Louise; Schnor, Peter; Grønbæk, Morten; Tolstrup, Janne S

    2017-12-01

    Visible age-related signs indicate biological age, as individuals that appear old for their age are more likely to be at poor health, compared with people that appear their actual age. The aim of this study was to investigate whether alcohol and smoking are associated with four visible age-related signs (arcus corneae, xanthelasmata, earlobe crease and male pattern baldness). We used information from 11 613 individuals in the Copenhagen City Heart Study (1976-2003). Alcohol intake, smoking habits and other lifestyle factors were assessed prospectively and visible age-related signs were inspected during subsequent examinations. The risk of developing arcus corneae, earlobe crease and xanthelasmata increased stepwise with increased smoking as measured by pack-years. For alcohol consumption, a high intake was associated with the risk of developing arcus corneae and earlobe crease, but not xanthelasmata. High alcohol consumption and smoking predict development of visible age-related signs. This is the first prospective study to show that heavy alcohol use and smoking are associated with generally looking older than one's actual age. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Ability of university-level education to prevent age-related decline in emotional intelligence.

    Science.gov (United States)

    Cabello, Rosario; Navarro Bravo, Beatriz; Latorre, José Miguel; Fernández-Berrocal, Pablo

    2014-01-01

    Numerous studies have suggested that educational history, as a proxy measure of active cognitive reserve, protects against age-related cognitive decline and risk of dementia. Whether educational history also protects against age-related decline in emotional intelligence (EI) is unclear. The present study examined ability EI in 310 healthy adults ranging in age from 18 to 76 years using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). We found that older people had lower scores than younger people for total EI and for the EI branches of perceiving, facilitating, and understanding emotions, whereas age was not associated with the EI branch of managing emotions. We also found that educational history protects against this age-related EI decline by mediating the relationship between age and EI. In particular, the EI scores of older adults with a university education were higher than those of older adults with primary or secondary education, and similar to those of younger adults of any education level. These findings suggest that the cognitive reserve hypothesis, which states that individual differences in cognitive processes as a function of lifetime intellectual activities explain differential susceptibility to functional impairment in the presence of age-related changes and brain pathology, applies also to EI, and that education can help preserve cognitive-emotional structures during aging.

  13. SOCIETAL COSTS ASSOCIATED WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN THE UNITED STATES.

    Science.gov (United States)

    Brown, Melissa M; Brown, Gary C; Lieske, Heidi B; Tran, Irwin; Turpcu, Adam; Colman, Shoshana

    2016-02-01

    The purpose of this study was to use a cross-sectional prevalence-based health care economic survey to ascertain the annual, incremental, societal ophthalmic costs associated with neovascular age-related macular degeneration. Consecutive patients (n = 200) with neovascular age-related macular degeneration were studied. A Control Cohort included patients with good (20/20-20/25) vision, while Study Cohort vision levels included Subcohort 1: 20/30 to 20/50, Subcohort 2: 20/60 to 20/100, Subcohort 3: 20/200 to 20/400, and Subcohort 4: 20/800 to no light perception. An interviewer-administered, standardized, written survey assessed 1) direct ophthalmic medical, 2) direct nonophthalmic medical, 3) direct nonmedical, and 4) indirect medical costs accrued due solely to neovascular age-related macular degeneration. The mean annual societal cost for the Control Cohort was $6,116 and for the Study Cohort averaged $39,910 (P societal ophthalmic costs, versus 74.1% of Control Cohort societal ophthalmic costs (P societal ophthalmic costs, versus 21.3% ($1,302/$6,116) of Control Cohort costs (P societal ophthalmic costs associated with neovascular age-related macular degeneration dramatically increase as vision in the better-seeing eye decreases.

  14. Guidelines for the Evaluation of Dementia and Age-Related Cognitive Change

    Science.gov (United States)

    American Psychologist, 2012

    2012-01-01

    Dementia in its many forms is a leading cause of functional limitation among older adults worldwide and will continue to ascend in global health importance as populations continue to age and effective cures remain elusive. The following guidelines were developed for psychologists who perform evaluations of dementia and age-related cognitive…

  15. A Longitudinal Study of Age-Related Differences in Reactions to Psychological Contract Breach

    NARCIS (Netherlands)

    Bal, P.M.; Lange, A.H. de; Jansen, P.G.W.; Velde, M.E.G. van der

    2013-01-01

    The current paper investigated age-related differences in the relations of psychological contract breach with work outcomes over time. Based on affective events theory, we expected job satisfaction to mediate the longitudinal relationship of contract breach with changes in job performance. Moreover,

  16. A longitudinal study of age-related differences in reactions to psychological contract breach

    NARCIS (Netherlands)

    Bal, P.M.; de Lange, A.H.; Jansen, P.G.W.; van der Velde, E.G.

    2013-01-01

    The current paper investigated age-related differences in the relations of psychological contract breach with work outcomes over time. Based on affective events theory, we expected job satisfaction to mediate the longitudinal relationship of contract breach with changes in job performance. Moreover,

  17. Age-related decrease in rod bipolar cell density of the human retina ...

    Indian Academy of Sciences (India)

    PRAKASH

    Age-related decrease in rod bipolar cell density of the human retina: an immunohistochemical study. P AGGARWAL, T C NAG and S WADHWA*. Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India. *Corresponding author (Fax, 91-11-26588663; Email, shashiwadhwa@hotmail.com).

  18. Significance of categorization and the modeling of age related factors for radiation protection

    International Nuclear Information System (INIS)

    Matsuoka, Osamu

    1987-01-01

    It is proposed that the categorization and modelling are necessary with regard to age related factors of radionuclide metabolism for the radiation protection of the public. In order to utilize the age related information as a model for life time risk estimate of public, it is necessary to generalize and simplify it according to the categorized model patterns. Since the patterns of age related changes in various parameters of radionuclide metabolism seem to be rather simple, it is possible to categorize them into eleven types of model patterns. Among these models, five are selected as positively significant models to be considered. Examples are shown as to the fitting of representative parameters of both physiological and metabolic parameter of radionuclides into the proposed model. The range of deviation from adult standard value is also analyzed for each model. The fitting of each parameter to categorized models, and its comparative consideration provide the effective information as to the physiological basis of radionuclide metabolism. Discussions are made on the problems encountered in the application of available age related information to radiation protection of the public, i.e. distribution of categorized parameter, period of life covered, range of deviation from adult value, implication to other dosimetric and pathological models and to the final estimation. 5 refs.; 3 figs.; 4 tabs

  19. The posterior parahippocampal gyrus is preferentially affected in age-related memory decline.

    NARCIS (Netherlands)

    Burgmans, S.; van Boxtel, M.P.J.; van den Berg, K.E.M.; Gronenschild, E.H.B.M.; Jacobs, H.I.L.; Jolles, J.; Uylings, H.B.M.

    2011-01-01

    Atrophy in the medial temporal lobe is generally considered to be highly associated with age-related memory decline. Volume loss in the hippocampus and entorhinal cortex has extensively been investigated, but the posterior parts of the parahippocampal gyrus have received little attention. The

  20. The posterior parahippocampal gyrus is preferentially affected in age-related memory decline

    NARCIS (Netherlands)

    Burgmans, S.; van Boxtel, M.P.J.; van den Berg, K.E.M.; Gronenschild, E.H.; Jacobs, H.I.L.; Jolles, J.; Uylings, H.B.M.

    2009-01-01

    Atrophy in the medial temporal lobe is generally considered to be highly associated with age-related memory decline. Volume loss in the hippocampus and entorhinal cortex has extensively been investigated, but the posterior parts of the parahippocampal gyrus have received little attention. The