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.

1. Synthesis, Modification and Turnover of Proteins during Aging
Suresh I.S. Rattan
Abstract
Introduction
Efficiency and Accuracy of Protein Synthesis during Aging
Altered Protein Synthesis during Aging
Post?Translational Modifications during Aging
Protein Turnover during Aging
Conclusion
2. Regulation of mRNA Translation as a Conserved Mechanism of Longevity Control
Ranjana Mehta, Devon Chandler?Brown, Fresnida J. Ramos, Lara S. Shamieh and Matt Kaeberlein
Abstract
Introduction
Genome Scale Longevity Screens in Yeast and Nematodes
mRNA Translation is a Public Determinant of Longevity
Is DR Mediated by Reduced mRNA Translation?
Possible Mechanisms for How Translation Influences Aging
Does mRNA Translation Modulate Aging in Mammals?
Conclusion
3. Protein Synthesis and the Antagonistic Pleiotropy Hypothesis of Aging
Pankaj Kapahi
Abstract
Evolution of Aging
Insulin?Like Signaling (ILS)
TOR Pathway
Protein Synthesis
Direct Screens to Identify Genes That Antagonistically Regulate Growth and Longevity
Dietary Restriction (DR), Protein Synthesis and Antagonistic Pleiotropy
Mechanism of Lifespan Extension by Inhibition of Protein Synthesis
Conclusion
4. Proteasome Function Determines Cellular Homeostasis and the Rate of Aging
Niki Chondrogianni and Efstathios S. Gonos
Abstract
Protein Homeostasis and Aging: Which Are the Key Players?
An Introduction to the Proteasome Biology
Proteasome during Aging
Proteasome Activation: Is There a Way to Restore Proteasome Function?
Conclusion
5. Autophagy and Longevity: Lessons from C. elegans
Kailiang Jia and Beth Levine
Abstract
Introduction
DAF?2 Insulin/IGF?1?Like Signaling
Dietary Restriction
Mitochondrial Activity
Autophagy
Autophagy and C. elegans Longevity Pathways
Conclusion
6. Autophagy and Aging: Lessons from Progeria Models
Guillermo Mariño, Alvaro F. Fernández and Carlos López?Otín
Abstract
Introduction
Autophagy and Physiological Aging
Autophagy and Premature Aging
Conclusion
7. Regulation of ProteinTurnover by Longevity Pathways
Tibor Vellai and Krisztina Takács?Vellai
Abstract
Protein Metabolism and Aging
Longevity Pathways That Promote Protein Synthesis
Interactions between Molecular Mechanisms Involved in Protein Synthesis and Degradation
Conclusion
8. Protein Metabolism and Lifespan in Caenorhabditis elegans
Geert Depuydt, Jacques R. Vanfleteren and Bart P. Braeckman
Abstract
Introduction
Dietary Restriction, TOR Signaling and Protein Homeostasis
Reduced Protein Synthesis Extends Lifespan
Translation Initiation
A Model for Translation Inhibition Induced Longevity
HSF?1 Mediated Defense against Proteotoxicity
Autophagy
Proteasome Function in Proteotoxicity and Longevity
Conclusion
9. Mitochondrial Protein Quality Control Systems in Aging and Disease
Karin Luce, Andrea C. Weil and Heinz D. Osiewacz
Abstract
Introduction
Mitochondrial Chaperones Are Necessary for Regulated Mitochondrial PQC
Role of the Mitochondrial Proteases in Maintaining Mitochondrial Functions
Role of the Membrane?Bound AAA Proteases on Diseases, Apoptosis and Aging
Mitochondrial Lon Protease Activity and Aging
Conclusion
10. p38MAPK in the Senescence of Human and Murine Fibroblasts
Florence Debacq?Chainiaux, Emmanuelle Boilan, Jérémie Dedessus Le Moutier, Geoffroy Weemaels and Olivier Toussaint
Abstract
Introduction
Senescence Is the Hardest Word to Say
The Role of DNA Damage Checkpoint Genes in Senescence
Signal Transduction and Gene Expression in SIPS: Central Role of p38MAPK
TGF?b1 and p38MAPK in H2O2? and UVB?Induced SIPS
p38MAPK, p53 and Rb
Role of Caveolin?1 in Cellular Senescence and Interplay with p38MAPK
Premature Senescence as an Anti?Oncogenic Defense Mechanism
Signaling Pathway Mediating Ras?Induced Premature Senescence¿ The Tumor Suppressing Function of p38MAPK
Conclusion: The Next Steps
11. Protein Homeostasis in Models of Aging and Age?Related Conformational Disease
Elise A. Kikis, Tali Gidalevitz and Richard I. Morimoto
Abstract
Protein Folding