Ageing Vulnerability

With the ever-increasing rise in life expectancy, there is an urgent need to improve our understanding of the relationship between ageing and the pathogenesis of age-related diseases in order to identify more effective means of prevention, amelioration and management of such diseases. In addition, there is a need to reduce the social and economic impact of the ageing population. Age-related morbidity and mortality vary dramatically among individuals; this book focusses on individual differences in susceptibility to age-related disorders.

It contains contributions from leading experts in the field on topics such as:
age-related pathology in the brain, age-related processes in stem cells, and age-related effects on the immune system and in bone, muscle and cardiovascular tissue.

For all those with an interest in the biology of ageing, this is compulsory reading.

In den letzten Jahren hat unser Wissen uber den menschlichen Alterungsproze? betrachlich zugenommen. Altersbedingte Erkrankungen und Sterblichkeit sind von Mensch zu Mensch sehr verschieden. Dieses Buch behandelt die individuellen Unterschiede und die Anfalligkeit fur altersbedingte Erkrankungen. Spezielle Kapitel widmen sich der altersbedingten Pathologie des Gehirns, altersbedingten Prozessen in den Stammzellen sowie altersbedingten Auswirkungen auf das Immunsystem, das Knochen-, Muskel und kardiovaskulare Gewebe.

Symposium on Ageing vulnerability: causes and interventions, held at the Novartis Foundation,
London, 29 February^3 March 2000

Editors: Gregory Bock (Organizer) and Jamie A. Goode

This symposium is based on a proposal made by Gary Andrews. It was organized as a key component and in support of the United Nations Project ‘A Research Agenda on Ageing for the 21st Century’
Thomas B. L. Kirkwood Introduction 1

Gary R. Andrews The priority of basic research on ageing vulnerability in a comprehensive research agenda on ageing for the 21st century 4

Discussion 9

Julie K. Andersen Do alterations in glutathione and iron levels contribute to pathology associated with Parkinson’s disease? 11

Discussion 20

Ashley I. Bush and Lee E. Goldstein Specific metal-catalysed protein oxidation reactions in chronic degenerative disorders of ageing: focus on Alzheimer’s disease and age-related cataracts 26

Discussion 38

General discussion I The role of glial cells in the ageing brain 44
R.N. Kalaria, C.G. Ballard, P.G. Ince, R.A. Kenny, I.G. McKeith, C.M. Morris, J.T. O’Brien, E. K. Perry, R.H. Perry and J. A. Edwardson Multiple substrates of late-onset dementia: implications for brain protection 49

Discussion 60

C. S. Potten, K. Martin and T. B. L. Kirkwood Ageing of murine small intestinal stem cells 66

Discussion 79

Amiela Globerson Haematopoietic stem cell ageing 85

Discussion 96

General discussion II 101

James K. Leung and Olivia M. Pereira-Smith Identification of genes involved in cell senescence and immortalization: potential implications for tissue ageing 105

Discussion 110

Jerry W. Shay and Woodring E.Wright Ageing and cancer: the telomere and telomerase connection 116

Discussion 125

Rita B. E¡ros Ageing and the immune system 130

Discussion 139

General discussion III 146

Lis Mosekilde Mechanisms of age-related bone loss 150

Discussion 166

Edward G. Lakatta, Steven J. Sollott and Salvatore Pepe The old heart: operating on the edge 172

Discussion 196

Anthony Cerami and Peter Ulrich Pharmaceutical intervention of advanced glycation end products 202

Discussion 212

General discussion IV 217

Holly Van Remmen, Zhongmao Guo and Arlan Richardson The anti-ageing action of dietary restriction 221

Discussion 230

D. A. Cottrell, E. L. Blakely, M. A. Johnson, G.M. Borthwick, P. I. Ince and D. M. Turnbull Mitochondrial DNA mutations in disease and ageing 234

Discussion 243

Douglas C. Wallace A mitochondrial paradigm for degenerative diseases and ageing 247

Discussion 263

Final discussion 267

Index of contributors 273

Subject index 275

The Novartis Foundation is an international scientific and educational charity which promotes the study and general knowledge of science and in particular encourages international co-operation in scientific research. Ageing at individual and population levels presents one of the greatest challenges to humankind as we enter this new century. Throughout the world today older adults are the fastest growing population groups. Mortality rates have declined in virtually all countries, raising the average life expectancy in the developing countries to the high 60s, and the high 70s in the developed world. Ageing is associated with an increased risk for development of chronic diseases that contribute to morbidity and mortality. It is estimated that by 2020 over two-thirds of deaths in the developing world will be caused by non-communicable diseases. This fact, along with the high levels of chronic morbidity associated with ageing in developed countries, represents a potentially overwhelming stress to health and social care systems globally.

The frontiers of knowledge in relation to human ageing have been pushed back in recent years and it is to be expected that continuous progress will be made towards understanding the basic ageing processes. Further research is now urgently needed to improve our understanding of the relationship between ageing and the pathogenesis of age-related diseases in order to identify more effective means of prevention, amelioration and management of such diseases, and reduce the social and economic impacts of population ageing and the related burden of age-associated morbidity.

Age-related morbidity and mortality differ dramatically in different individuals. The focus of this book is on individual differences in susceptibility to age-related disorders. Specific chapters in the book deal with age-related pathology in the brain, age-related processes in stem cells, and age-related effects on the immune system and in bone, muscle and cardiovascular tissue. Bringing together the leading researchers in the ageing field to discuss their work, this book is compulsory reading for all those interested in the biology of ageing.