Advances in Stem Cell Aging

Advances in Stem Cell Aging

Else Kröner-Fresenius Symposia Vol. 3 Series Editor S. Pahernik Heidelberg

Advances in Stem Cell Aging Volume Editor Karl Lenhard Rudolph Ulm 20 figures in color, 2012 Basel Freiburg Paris London New York New Delhi Bangkok Beijing Tokyo Kuala Lumpur Singapore Sydney

Karl Lenhard Rudolph Leibniz Institute for Age Research Fritz-Lipmann Institute (FLI) Jena and University of Ulm Institute of Molecular Medicine and Max Planck Research Group on Stem Cell Aging Life Science Building, N27, Room 4015 James-Frank-Ring DE 89081 Ulm This book is sponsored by the Else Kröner-Fresenius-Stiftung. Library of Congress Cataloging-in-Publication Data Advances in stem cell aging / volume editor, Karl Lenhard Rudolph. p. ; cm. -- (Else Kröner-Fresenius symposia, ISSN 1663-0114 ; vol. 3) Includes bibliographical references and indexes. ISBN 978-3-318-02170-7 (hard cover : alk. paper) -- ISBN 978-3-318-02171-4 (electronic version) I. Rudolph, K. Lenhard. II. Series: Else Kröner-Fresenius symposia; v. 3. ; 1663-0114. [DNLM: 1. Adult Stem Cells--physiology--Congresses. 2. Cell Aging--genetics--Congresses. 3. DNA Damage--physiology--Congresses. 4. Telomere--genetics--Congresses. QU 325] 616.02 774--dc23 2012024102 Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents. Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book 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. 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 change 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. 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. Cover art by Maren Blaschke Copyright 2012 by S. Karger AG, P.O. Box, CH 4009 Basel (Switzerland) www.karger.com Printed in Germany on acid-free and non-aging paper (ISO 9706) by Kraft Druck, Ettlingen ISSN 1663 0114 ISBN 978 3 318 02170 7 eisbn 978 3 318 02171 4

Contents VII Preface Pahernik, S. (Heidelberg) 1 Introduction Rudolph, K.L. (Ulm) Chapter 1 2 Speakers at the Symposium Morita, M. (Ulm) Chapter 2 18 Aging of the Niche and the Microenvironment and Its Role in Stem Cell Aging Geiger, H. (Ulm) Chapter 3 27 Hematopoietic Stem Cell Aging and Cancer Chen, Y.; Ju, Z. (Hangzhou) Chapter 4 36 DNA Damage, Checkpoint Responses, and Cell Cycle Control in Aging Stem Cells Kleinhans, K.N.; Burkhalter, M.D. (Ulm) Chapter 5 48 Hematopoietic Stem Cell Aging and Fate Decision Illing, A.; Morita, Y. (Ulm) V

Chapter 6 74 Stem Cell Therapy and Stress Response in Pancreas and Intestine Sperka, T.; Omrani, O. (Ulm) Chapter 7 87 Niche-Stem Cell Interations and Environmental Influences Tang, D. (Ulm) Chapter 8 92 Stem Cells and Metabolism Missios, P.; Guachalla, L. (Ulm) Chapter 9 100 Molecular Mechanisms of Muscle Stem Cell Aging Baig, A.H.; Tümpel, S. (Ulm) Chapter 10 112 Neural Stem Cells in Development and Aging Schmidt-Straßburger, U. (Ulm) 121 Author Index 122 Subject Index VI

Preface Advances in Stem Cell Aging This book series features the proceedings of the Else Kröner-Fresenius Symposia, which are intended to cover clinically relevant topics at the forefront of biomedical research. The meetings should give experts the opportunity to discuss the most recent findings in evolving fields of biomedicine and outline future research strategies. Today s research is characterized by the accelerated generation of biomedical data, the increasingly interdisciplinary and translational nature of biomedical science, as well as efforts to integrate the data into complex biological systems. These developments emphasize the need for new forums of discussion. The understanding of stem cell aging in the context of other tissue and malignant tumors is highly relevant for future developments in biomedicine. Physiology, modulation, and pathology promise new perspectives in restoring organ function lost by disease or physical trauma and in overcoming pathophysiological conditions. In this context, following the first Else Kröner- Fresenius Symposium held in May 2009 focusing on stem cell aging at the cellular and molecular level, Dr. Karl Lenhard Rudolph organized the 3rd Else Kröner-Fresenius Symposium in May 2011, with world renown experts discussing current advances of cell stem aging and illustrating new perspectives integrating diverse fields of stem cell research. The Else Kröner-Fresenius-Stiftung thanks Dr. Rudolph for his inspiring scientific work and personal outstanding input for organizing, together with his team, the 3rd Else Kröner-Fresenius Symposium. The Else Kröner-Fresenius-Stiftung In 1983, Else Kröner (1925 1988) founded the Else Kröner-Fresenius-Stiftung, a nonprofit foundation dedicated to promoting medical science, supporting medical education, and providing humanitarian aid. Else Kröner, born Fernau, was born on May 15, 1925, in Frankfurt am Main, Germany. At the age of 3 years, her father died. After his death, she lived with her mother in the home of Dr. Eduard Fresenius, a pharmacist and owner of the Hirsch Pharmacy in Frankfurt, who founded the pharmaceutical company Fresenius in 1912. Dr. Eduard Fresenius, whose marriage was childless,

took care of Else Fernau. In 1944, she started an internship at the Hirsch Pharmacy and decided to study pharmacy, which was supported by Dr. Eduard Fresenius. In 1946, Dr. Eduard Fresenius unexpectedly died. At that time, Else Fernau had not completed her pharmaceutical education. However, Dr. Eduard Fresenius bequeathed the Hirsch Pharmacy and the Fresenius company to her. At the age of 21 years, Else Fernau decided, against the council of many, to take responsibility for the Hirsch Pharmacy and the Fresenius company. At that time, the Fresenius company was completely indebted. Of the original 400 employees, all but 30 had to be laid off. She joined efforts in the early 1950s with her later husband, Hans Kröner, a lawyer and economist, to ensure the survival and force the expansion of the company. The company was progressively rebuilt. At that time, the need to maintain the company determined all activities. Entrepreneurial important and far-sighted business decisions in the 1950s and 1960s ensured the successful future development of the company. Decades of growth followed, in particular within the field of dialysis, nutrition and intensive care, leading to an internationally competitive enterprise and market leader in special areas of health care. Until 1981, Else Kröner led the company. After the transformation of Fresenius into a stock company, Else Kröner remained chairman of the Supervisory Board until her death on June 5, 1988. From 1981 to 1992, her husband Hans Kröner led the company as CEO. Thereafter, he significantly influenced the policy of the Else Kröner-Fresenius-Stiftung, of which he was chairman of the board from 1995 to 2005. Today, the Fresenius group, of which the Else Kröner-Fresenius-Stiftung is the leading share holder, is an international healthcare group with products and services for dialysis, hospital, and medical care of patients. The Fresenius group currently employs nearly 150,000 people in over 100 countries and generates annual sales of over EUR 16 billion. Else Kröner transferred nearly her entire fortune to the foundation for the pursuit of promoting medical science and providing humanitarian aid. It corresponds to her requests and represents the continuation of her concept that her fortune be used for nonprofit purposes. The symposia are published as part of the foundation s commitment to the advancement of medical research and treatment. Sascha Pahernik, Heidelberg Member of the Scientific Committee of the Else Kröner-Fresenius-Stiftung Series Editor VIII Preface