Protein Metabolism and Homeostasis in Aging
:
Nektarios Tavernarakis
:
Nektarios Tavernarakis
:
Protein Metabolism and Homeostasis in Aging
:
Springer-Verlag
:
9781441970022
:
Advances in Experimental Medicine and Biology
:
1
:
CHF 135.30
:
:
Nichtklinische Fächer
:
English
:
248
:
Wasserzeichen
:
PC/MAC/eReader/Tablet
:
PDF
Aging is loosely defined as the accumulation of changes in an organism over time. At the cellular level such changes are distinct and multidimensional: DNA replication ceases, cells stop dividing, they become senescent and eventually die. DNA metabolism and chromosomal maintenance, together with protein metabolism are critical in the aging process. The focus of this book is on the role of protein metabolism and homeostasis in aging. An overview is provided of the current knowledge in the area, including protein synthesis, accuracy and repair, post-translational modifications, degradation and turnover, and how they define and influence aging. The chapters mainly focus on well-characterised factors and pathways, but new areas are also presented, where associations with aging are just being elucidated by current experimental data. Protein turnover, the balance between protein synthesis and protein degradation are carefully maintained in healthy cells. Chapters 1 and 2 illustrate that aging cells are characterised by alterations in the rate, level and accuracy of protein synthesis compared to young ones, and that mRNA translation, essential for cell growth and survival, is controlled at multiple levels. The theory that growth and somatic maintenance are believed to be antagonistic processes is described in Chapter 3: inhibition of protein synthesis results in decreased rates of growth and development, but also confers an extension of lifespan, as shown for example by the effects of dietary restriction in various models organisms.
Nektarios Tavernarakis is a Research Director (Professor) at the Institute of Molecular Biology and Biotechnology, in Heraklion, Crete, Greece, heading the Caenorhabditis elegans molecular genetics laboratory. He earned his PhD degree at the University of Crete, studying gene expression regulation in yeast, and trained in C. elegans genetics and molecular biology at Rutgers University, New Jersey, USA. His research focuses on studies of neuronal function and dysfunction, using the nematode Caenorhabditis elegans as a model organism. His main interests are the molecular mechanisms of necrotic cell death in neurodegeneration and senescent decline, the molecular mechanisms of sensory transduction and integration by the nervous system, the interplay between cellular metabolism and aging, and the development of novel genetic tools for C. elegans research. He is the recipient of a European Research Council (ERC ) Advanced Investigator grant award, a European Molecular Biology Organisation (EMBO) Young Investigator award, an International Human Frontier in Science Program Organization (HF SPO) long-term award, the Bodossaki Foundation Scientific Prize for Medicine and Biology, the Alexander von Humboldt Foundation, Friedrich Wilhelm Bessel research award, and is member of EMBO.
Title Page
3
Copyright Page
4
DEDICATION
5
PREFACE
6
ABOUT THE EDITOR...
8
PARTICIPANTS
9
Table of Contents
13
ACKNOWLEDGEMENTS
18
Chapter 1 Synthesis, Modification and Turnoverof Proteins during Aging
19
Introduction
19
Efficiency and Accuracy of Protein Synthesis during Aging
19
Altered Protein Synthesis during Aging
20
Post-Translational Modifications during Aging
22
Phosphorylation
22
Oxidation
23
Glycation
24
Deamidation, Racemization and Isomerization
24
ADP-Ribosylation
25
Methylation
25
Proteolytic Processing
26
Other Modifications
26
Protein Turnover during Aging
27
Conclusion
27
References
27
Chapter 2 Regulation of mRNA Translationas a Conserved Mechanismof Longevity Control
32
Introduction
32
Genome Scale Longevity Screens in Yeast and Nematodes
34
mRNA Translation is a Public Determinant of Longevity
35
Is DR Mediated by Reduced mRNA Translation?
35
Possible Mechanisms for How Translation Influences Aging
38
Does mRNA Translation Modulate Aging in Mammals?
41
mRNA Translation and Cancer
41
mRNA Translation and Diabetes
42
mRNA Translation and Cardiovascular Disease
42
mRNA Translation and Neurodegenerative Disease
42
Conclusion
43
References
43
Chapter 3 Protein Synthesis and the AntagonisticPleiotropy Hypothesis of Aging
48
Evolution of Aging
48
Insulin-Like Signaling (ILS)
49
TOR Pathway
49
Protein Synthesis
50
Direct Screens to Identify Genes That Antagonistically Regulate Growth and Longevity
50
Dietary Restriction (DR), Protein Synthesis and Antagonistic Pleiotropy
51
Mechanism of Lifespan Extension by Inhibition of Protein Synthesis
52
Conclusion
53
References
53
Chapter 4 Proteasome Function DeterminesCellular Homeostasis and the Rateof Aging
56
Protein Homeostasis and Aging: Which Are the Key Players?
56
An Introduction to the Proteasome Biology
57
Proteasome during Aging
59
Proteasome Activation: Is There a Way to Restore Proteasome Function?
60
Genetic Activation of the Proteasome
60
Proteasome Activation by Natural or Chemical Compounds
60
In Vivo Evidence of Proteasome Activation
61
Conclusion
62
References
62
Chapter 5 Autophagy and Longevity:Lessons from C. elegans
65
Introduction
65
DAF-2 Insulin/IGF-1-Like Signaling
66
Dietary Restriction
70
Mitochondrial Activity
70
Autophagy
71
Autophagy and C. elegans Longevity Pathways
72
Conclusion
75
References
75
Chapter 6 Autophagy and Aging:Lessons from Progeria Models
79
Introduction
79
Autophagy and Physiological Aging
80
Autophagy and Premature Aging
82
Conclusion
84
References
84
Chapter 7 Regulation of Protein Turnoverby Longevity Pathways
87
Protein Metabolism and Aging
87
Longevity Pathways That Promote Protein Synthesis
92
Insulin/IGF-1 Signaling
92
TOR Signaling
93
RAS/ERK Signaling
94
TGF-ß Signaling
94
JNK Kinase-Mediated Signaling
94
Mitochondrial Respirtory Chain
95
Interactions between Molecular Mechanisms Involved in Protein Synthesis and Degradation
95
Conclusion
96
References
97
Chapter 8 Protein Metabolism and Lifespanin Cae
