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      Can the Immune System Still Be Efficient in the Elderly? An Immunological and Immunoendocrine Therapeutic Perspective

      review-article
      a, b , a
      Neuroimmunomodulation
      S. Karger AG
      Aging, T cells, Thymus, B cells, Immunosenescence, Inflammation

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          Abstract

          The continuous global increase in life expectancy represents a central challenge for our society and impacts public social security systems, families and individuals. One of the most striking changes that occur during normal human aging is immunosenescence, a progressive and overall diminution of immune functions that affect all cells and organs of the innate and adaptive immune system. As a hallmark of human aging, the progressive involution of the thymus leads to a disturbed balance and function of naïve, memory and effector T cells, thus promoting a latent pro-inflammatory status in the elderly. Together with chronic infections such as cytomegalovirus, that accumulate during life, this situation manifests in clinically relevant implications such as poor overall immune responses, decreased ability to control infectious disease and diminished response to vaccinations. Interestingly, this process parallels changes in the hormonal balance of aging subjects. In this review, we summarize recently published intriguing results from a very active and growing field of biomedical research and discuss some clinical consequences as well as possible ways of immune- and/or hormone-based interventions to delay or reverse immunosenescence.

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          Most cited references100

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          A pilot study of enhanced depth imaging optical coherence tomography of the choroid in normal eyes.

          To measure macular choroidal thickness in normal eyes at different points using enhanced depth imaging (EDI) optical coherence tomography (OCT) and to evaluate the association of choroidal thickness and age. Retrospective, observational case series. EDI OCT images were obtained in patients without significant retinal or choroidal pathologic features. The images were obtained by positioning a spectral-domain OCT device close enough to the eye to acquire an inverted image. Seven sections were obtained within a 5 x 30-degree area centered at the fovea, with 100 scans averaged for each section. The choroid was measured from the outer border of the retinal pigment epithelium to the inner scleral border at 500-microm intervals of a horizontal section from 3 mm temporal to the fovea to 3 mm nasal to the fovea. Statistical analysis was performed to evaluate variations of choroidal thickness at each location and to correlate choroidal thickness and patient age. The mean age of the 30 patients (54 eyes) was 50.4 years (range, 19 to 85 years), and 14 patients (46.7%) were female. The choroid was thickest underneath the fovea (mean, 287 microm; standard deviation, +/- 76 microm). Choroidal thickness decreased rapidly in the nasal direction and averaged 145 microm (+/- 57 microm) at 3 mm nasal to the fovea. Increasing age was correlated significantly with decreasing choroidal thickness at all points measured. Regression analysis suggested that the subfoveal choroidal thickness decreased by 15.6 microm for each decade of life. Choroidal thickness seems to vary topographically within the posterior pole. The thickness of the choroid showed a negative correlation with age. The decrease in the thickness of the choroid may play a role in the pathophysiologic features of various age-related ocular conditions.
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            Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: a possible mechanism for RPE aging and age-related macular degeneration.

            Oxidative stress is believed to contribute to the pathogenesis of many diseases, including age-related macular degeneration (AMD). Although the vision loss of AMD results from photoreceptor damage in the central retina, the initial pathogenesis involves degeneration of RPE cells. Evidence from a variety of studies suggests that RPE cells are susceptible to oxidative damage. Mitochondrial DNA (mtDNA) is particularly prone to oxidative damage compared to nuclear DNA (nDNA). Using the quantitative PCR assay, a powerful tool to measure oxidative DNA damage and repair, we have shown that human RPE cells treated with H(2)O(2) or rod outer segments resulted in preferential damage to mtDNA, but not nDNA; and damaged mtDNA is not efficiently repaired, leading to compromised mitochondrial redox function as indicated by the MTT assay. Thus, the susceptibility of mtDNA to oxidative damage in human RPE cells, together with the age-related decrease of cellular anti-oxidant system, provides the rationale for a mitochondria-based model of AMD.
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              Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells.

              Despite the importance of thymic stromal cells to T-cell development, relatively little is known about their biology. Here, we use single-cell analysis of stromal cells to analyze extensive changes in the number and composition of thymic stroma throughout life, revealing a surprisingly dynamic population. Phenotypic progression of thymic epithelial subsets was assessed at high resolution in young mice to provide a developmental framework. The cellular and molecular requirements of adult epithelium were studied, using various mutant mice to demonstrate new cross talk checkpoints dependent on RelB in the cortex and CD40 in the medulla. With the use of Ki67 and BrdU labeling, the turnover of thymic epithelium was found to be rapid, but then diminished on thymic involution. The various defects in stromal turnover and composition that accompanied involution were rapidly reversed following sex steroid ablation. Unexpectedly, mature cortical and medullary epithelium showed a potent capacity to stimulate naive T cells, comparable to that of thymic dendritic cells. Overall, these studies show that the thymic stroma is a surprisingly dynamic population and may have a more direct role in negative selection than previously thought.
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                Author and article information

                Journal
                NIM
                Neuroimmunomodulation
                10.1159/issn.1021-7401
                Neuroimmunomodulation
                S. Karger AG
                978-3-8055-8979-6
                978-3-8055-8980-2
                1021-7401
                1423-0216
                2008
                November 2008
                26 November 2008
                : 15
                : 4-6
                : 351-364
                Affiliations
                aLaboratory on Thymus Research and bMulticolor Flow Cytometry Platform, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
                Article
                156477 Neuroimmunomodulation 2008;15:351–364
                10.1159/000156477
                19047811
                02ffe862-2e11-4e2a-98f5-03574828355b
                © 2008 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                Figures: 2, Tables: 3, References: 166, Pages: 14
                Categories
                Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Thymus,Aging,Inflammation,Immunosenescence,T cells,B cells

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