Telomeres and Telomerase in Aging, Disease, and Cancer: Molecular Mechanisms of Adult Stem Cell Ageing

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K. Lenhard Rudolph
Springer Science & Business Media, 2007 M11 7 - 330 páginas
Twenty-five years after the disclosure of the telomeric DNA sequence and 22 years after the discovery of telomerase, it has become clear that telomeres and telomerase influence disease of human ageing including cancer. This book summarizes our current knowledge on the role of telomeres and telomerase in ageing, regeneration, and cancer with a special focus on ageing stem cells. Moreover, the book reviews current ef forts to target telomeres and telomerase for anticancer treatment or reg- erative therapies. 1. 1 Ageing The molecular analysis of ageing is an emerging research field that will have great impact on patients care, lifestyle, and on disease prevention in the human population worldwide. Major molecular mechanisms that influence the ageing process include (1) the accumulation of molecular damage affecting DNA and p- teins, (2) alterations in gene expression, including alterations in checkpoint responses, metabolic pathways, and developmental pathways, and (3) the decline in adult stem cell function. All these mechanisms lead to a decrease in organ main- nance and function, thus representing a major factor limiting the quality of life d- ing ageing. Moreover, the accumulation of molecular damage increases genetic alterations and the cancer risk during ageing. Indeed, increased age is the leading cause of cancer. Understanding the molecular basis of ageing will ultimately point to targets for novel therapies aiming to improve the function of cells and organs in the ageing organism, thus allowing increased vitality or what we think of as “healthy ageing.
 

Contenido

Cellular versus Organismal Aging
3
TelomereInduced Senescence of Primary Cells
23
Telomeres Senescence Oxidative Stress and Heterogeneity
43
Initiation of Genomic Instability Cellular Senescence
57
Telomerase Mutations and Premature Ageing in Humans 77
76
Mechanisms of Stem Cell Ageing 111
109
Senescence Signatures of Human Hematopoietic Stem Cells
141
Telomere Shortening Induces Cell Intrinsic Checkpoints
161
Alan E Bilsland
178
A TelomereIndependent
181
Telomerase as a Potential Regulator of Tissue
203
Telomere Shortening and Telomerase Activation during
212
Telomere Binding Proteins and Disease
229
Therapeutic Options
247
Index
309
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