The Quail Mesonephros: A New Model for Renal Senescence?

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Abstract

Background/Aims: Renal senescence during normal aging is associated with specific vascular alterations and tissue degeneration. Although the degenerative program executed during embryonic kidney development is known to include vascular alterations, studies yet have to examine whether it involves replicative senescence. In this study, we assessed the potential of the quail mesonephros, a transitory embryonic kidney, as a model of human renal senescence. Methods: Quail embryos with developing or degenerating mesonephros were studied on day 6 or day 11 of incubation, respectively. Senescence-associated β-galactosidase activity, a marker of replicative senescence, was examined on whole mounts and sections. Senescent vascular characterization was performed by the scanning electron-microscopic analysis of vascular corrosion casts. Results: Senescence-associated β-galactosidase activity was found only in old mesonephros. Moreover, at 11 days of incubation glomerular capillaries showed discontinuities and were thinner and more tortuous than those observed at 6 days, characteristics also reported for the aging human kidney. Conclusion: The degenerating quail mesonephros is a potential model of renal senescence, showing biochemical and morphological characteristics of the aging human kidney.

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Most cited references 14

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A series of normal stages in the development of the chick embryo

Viktor Hamburger, Howard L. Hamilton (1951)

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Replicative senescence of human endothelial cells in vitro involves G1 arrest, polyploidization and senescence-associated apoptosis.

Mechthild Wagner, Barbara Hampel, David Bernhard … (2001)

Human ageing is characterized by a progressive loss of physiological functions, increased tissue damage and defects in various tissue renewal systems. Age-related decreases of the cellular replicative capacity can be reproduced by in vitro assays of cellular ageing. When diploid human fibroblasts reach their finite lifespan, they enter an irreversible G1 growth arrest status referred to as replicative senescence. While deregulation of programmed cell death (apoptosis) is a key feature of age-related pathology in several tissues, this is not reflected in the standard in vitro senescence model of human fibroblasts, and the role of apoptosis during cellular ageing remains unclear. We have analyzed replicative senescence of human umbilical vein endothelial cells (HUVEC) in vitro and found that senescent HUVEC also arrest in the G1 phase of the cell cycle but, unlike fibroblasts, accumulate with a 4N DNA content, indicative of polyploidization. In contrast to human fibroblasts, senescent endothelial cells display a considerable increase in spontaneous apoptosis. The data imply that age-dependent apoptosis is a regular feature of human endothelial cells and suggest cell type specific differences in human ageing.

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Differential regulation of apoptotic cell death in senescent human cells.

Barbara Hampel, Florence Malisan, Harald Niederegger … (2015)

Aging of human cells can be reproduced in monolayer cultures, revealing the phenotype of replicative senescence. It was shown that diploid human fibroblasts enter a stable growth arrest phenotype at the end of their lifespan and, in particular, these cells are resistant to various apoptotic stimuli. In contrast, human endothelial cells from the umbilical vein (HUVEC) acquire a proapoptotic phenotype when reaching senescence and this probably results from reactive oxygen species (ROS) induced damage and associated signaling. Ceramides were shown to accumulate in senescent fibroblasts and are also known as potent regulators of apoptotic cell death. To further study age-associated changes in proneness to apoptosis between fibroblasts and endothelial cells, both cell types were challenged by administration of exogenous ceramide and apoptotic cell death was determined. While ceramide can efficiently induce apoptosis in both young and senescent cells of either histotype, quantitative evaluation of the data show that senescent fibroblasts are more resistant to apoptosis induction when compared to their young counterparts, whereas in the case of endothelial cells proneness for apoptosis is increased in senescent cells. Together, these data suggest significant differences in the regulation of apoptosis associated with senescence in fibroblasts and endothelial cells.

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Author and article information

Journal

Journal ID (publisher-id): JVR

Journal ID (nlm-ta): J Vasc Res

Journal ID (doi): 10.1159/issn.1018-1172

Title: Journal of Vascular Research

Publisher: S. Karger AG

ISSN (Print): 1018-1172

ISSN (Electronic): 1423-0135

Publication date Subscription-year: 2006

Publication date (Print): November 2006

Publication date (Electronic): 03 November 2006

Volume: 43

Issue: 6

Pages: 581-586

Affiliations

^aCenter of Animal Biotechnology and Gene Therapy (CBATEG), ^bDepartment of Animal Health and Anatomy, School of Veterinary Medicine, ^cDepartment of Morphology, Faculty of Medicine, and ^dDepartment of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, and ^eLaboratory of Experimental Nephrology, Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Hospital de Bellvitge, L‘Hospitalet de Llobregat, Spain

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Publisher ID: 96076 Other ID: J Vasc Res 2006;43:581–586

DOI: 10.1159/000096076

PubMed ID: 17028443

SO-VID: aa0ea907-36a1-495b-ba22-74ec302c9c89

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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

Date received : 30 June 2006

Date accepted : 05 August 2006

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Figures: 3, References: 23, Pages: 6

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The Quail Mesonephros: A New Model for Renal Senescence?

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Karger: Cardiovascular System

Most cited references 14

A series of normal stages in the development of the chick embryo

Replicative senescence of human endothelial cells in vitro involves G1 arrest, polyploidization and senescence-associated apoptosis.

Differential regulation of apoptotic cell death in senescent human cells.

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