Senescence Edited by Tetsuji Nagata SENESCENCE Edited by Tetsuji Nagata INTECHOPEN.COM Senescence http://dx.doi.org/10.5772/1905 Edited by Tetsuji Nagata Contributors John N. Buchholz, Conwin Vanterpool, William Pottorf, Erik J. Behringer, Sue Duckles, David Delmail, Pascal Labrousse, Thiago Monaco, Paulo Silveira, Daniel Silvestre, Keith Wheaton, Carmelo Bernabeu, Francisco Javier Blanco, Miloud Hafsi, Ali Guendouz, Judit Pongracz, Krisztian Kvell, Giovanni Scapagnini, Calogero Caruso, Sergio Davinelli, Davide Zella, Vasto, Diego Julio Arenas-Aranda, Elena Hernández-Caballero, Fabio Salamanca-Gómez, Eileen Anne McLaughlin, Alexander Peter Sobinoff, Ilana Bernstein, Norio Wake, Takafumi Inoue, Kayoko Maehara, Gang Lu, Jing- Ye Zhou, Yong Yu, Xian-Lun Zhu, Chi-Ping Ng, Wai-Sang Poon, Nouha Domloge, Karine Cucumel, Jean Marie Botto, Claude Dal Farra, Milena Atanasova, Anelia Aleksandrova Dimitrova, Boryana Krumova Ruseva, Angelina Stoyanova, Miglena Georgieva, Emiliana Konova, Maria Crisan, Diana Crisan, Jaba Tkemaladze, Alexandre Tavartkiladze, Konstantin Chichinadze, Pascual Medina, Susana Novella, Carlos Hermenegildo, Gloria Segarra, Ana Paula Dantas, Eloísa Agüera, Purificación De La Haba, Purificación Cabello, Estefanía Molina, Lourdes De La Mata, Antonio Paolo Beltrami, Daniela Cesselli, Angela Caragnano, Natascha Bergamin, Veronica Zanon, Nicoletta Finato, Carlo Alberto Beltrami, Hulya Yucel, Anna Freixas, Barbara Luque, Amalia Reina, Jean-François Rontani, Brun Ulfhake, Mikael Altun, Max Gronholdt-Klein, Lingzhan Wang, Patrizia d’Alessio, Pierre Frendo, Laurence Dupont, Geneviève Alloing, Sarra El Msehli, Olivier Pierre, Julie Hopkins, Didier Hérouart, Ulrike Zentgraf, Ross Hannan, Jorge Rabinovich, Paula Medone, Frédéric Menu, Soledad Ceccarelli, Delmi Margarita Canale, Eliana Nieves, Raúl L. Stariolo, Kieron Edwards, Juan Pablo Sanchez-Tamburrino, Matt Humphry, Paula Fernandez, Sebastian Moschen, Norma Paniego, Ruth Heinz, Tetsuji Nagata, Teimuraz Lezhava, Jamlet Monaselidze, Tinatin Jokhadze © The Editor(s) and the Author(s) 201 2 The moral rights of the and the author(s) have been asserted. All rights to the book as a whole are reserved by INTECH. The book as a whole (compilation) cannot be reproduced, distributed or used for commercial or non-commercial purposes without INTECH’s written permission. Enquiries concerning the use of the book should be directed to INTECH rights and permissions department (permissions@intechopen.com). Violations are liable to prosecution under the governing Copyright Law. 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The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. First published in Croatia, 2012 by INTECH d.o.o. eBook (PDF) Published by IN TECH d.o.o. Place and year of publication of eBook (PDF): Rijeka, 2019. IntechOpen is the global imprint of IN TECH d.o.o. Printed in Croatia Legal deposit, Croatia: National and University Library in Zagreb Additional hard and PDF copies can be obtained from orders@intechopen.com Senescence Edited by Tetsuji Nagata p. cm. ISBN 978-953-51-0144-4 eBook (PDF) ISBN 978-953-51-4340-6 Selection of our books indexed in the Book Citation Index in Web of Science™ Core Collection (BKCI) Interested in publishing with us? Contact book.department@intechopen.com Numbers displayed above are based on latest data collected. For more information visit www.intechopen.com 4,000+ Open access books available 151 Countries delivered to 12.2% Contributors from top 500 universities Our authors are among the Top 1% most cited scientists 116,000+ International authors and editors 120M+ Downloads We are IntechOpen, the world’s leading publisher of Open Access books Built by scientists, for scientists Meet the editor Tetsuji Nagata, M.D, Ph.D, Professor Emeritus (Depart- ment of Anatomy and Cell Biology, Shinshu University School of Medicine, Matsumoto, and Department of Anatomy, Shinshu Institute of Alternative Medicine and Welfare, Nagano) was Born in Nagano, Japan, Febru- ary 5, 1931. After high school he finished premedical course at Shinshu University College of Liberal Arts and Sciences; medical education at Shinshu University School of Medicine, Matsumoto, Japan, 1951-1955. He received his PhD in Anatomy 1961., also at Shinshu University Graduate School of Medicine, Matsumoto, Japan. Dr. Nagata received several awards and honors. He is author of 10 sin- gle-authored books and 112 co-authored books, 586 original and review papers, 713 contributed papers at national and international conferences in Asian-Pacific, European and American countries. Contents Part 1 Plant 1 Chapter 1 Photo- and Free Radical-Mediated Oxidation of Lipid Components During the Senescence of Phototrophic Organisms 3 Jean-François Rontani Chapter 2 Role of Intracellular Hydrogen Peroxide as Signalling Molecule for Plant Senescence 31 Ulrike Zentgraf, Petra Zimmermann and Anja Smykowski Chapter 3 Metabolic Regulation of Leaf Senescence in Sunflower ( Helianthus annuus L.) Plants 51 Eloísa Agüera, Purificación Cabello, Lourdes de la Mata, Estefanía Molina and Purificación de la Haba Chapter 4 Functional Approaches to Study Leaf Senescence in Sunflower 69 Paula Fernandez, Sebastián Moschen, Norma Paniego and Ruth A. Heinz Chapter 5 Plant Ageing, a Counteracting Agent to Xenobiotic Stress 89 David Delmail and Pascal Labrousse Chapter 6 Some Aspects of Leaf Senescence 107 Hafsi Miloud and Guendouz Ali Chapter 7 Advances in Plant Senescence 117 Kieron D. Edwards, Matt Humphry and Juan Pablo Sanchez-Tamburrino Chapter 8 The Legume Root Nodule: From Symbiotic Nitrogen Fixation to Senescence 137 Laurence Dupont, Geneviève Alloing, Olivier Pierre, Sarra El Msehli, Julie Hopkins, Didier Hérouart and Pierre Frendo Preface XIII X Contents Part 2 Animal 169 Chapter 9 The Nucleolus and Ribosomal Genes in Aging and Senescence 171 Nadine Hein, Elaine Sanij, Jaclyn Quin, Katherine M. Hannan, Austen Ganley and Ross D. Hannan Chapter 10 Senescence in Animals: Why Evolutionary Theories Matter 209 Thiago Monaco, Daniel Silvestre and Paulo S. P. Silveira Chapter 11 The Quest for Immortality in Triatomines: A Meta-Analysis of the Senescence Process in Hemimetabolous Hematophagous Insects 225 Paula Medone, Jorge Rabinovich, Eliana Nieves, Soledad Ceccarelli, Delmi Canale, Raúl L. Stariolo and Frédéric Menu Chapter 12 Programming and Implementation of Age-Related Changes 251 Jaba Tkemaladze, Alexander Tavartkiladze and Konstantin Chichinadze Chapter 13 Cellular Degradation Machineries in Age-Related Loss of Muscle Mass (Sarcopenia) 269 Mikael Altun, Max Grönholdt-Klein, Lingzhan Wang and Brun Ulfhake Chapter 14 Cell Senescence as Observed by Electron Microscopic Radioautography 287 Tetsuji Nagata Chapter 15 Macromolecular Synthesis in the Digestive and Respiratory Systems 315 Tetsuji Nagata Chapter 16 Macromolecular Synthesis in the Urinary and Reproductive Systems 359 Tetsuji Nagata Chapter 17 Macromolecular Synthesis in the Endocrine, Nervous and Sensory Systems 387 Tetsuji Nagata Chapter 18 Cellular Senescence and Its Relation with Telomere 439 Diego Julio Arenas-Aranda, Elena Hernández-Caballero and Fabio Salamanca-Gómez Chapter 19 Caveolar Vesicles in Cellular Senescence 463 Keith Wheaton Contents XI Chapter 20 Alternative Splicing in Endothelial Senescence: Role of the TGF- β Co-Receptor Endoglin 499 Francisco J. Blanco and Carmelo Bernabéu Chapter 21 Quantification of Elastin, Collagen and Advanced Glycation End Products as Functions of Age and Hypertension 519 Milena Atanasova, Aneliya Dimitrova, Boryana Ruseva, Angelina Stoyanova, Miglena Georgieva and Emiliana Konova Chapter 22 Calcium Regulation in Neuronal Function with Advancing Age: Limits of Homeostasis 531 John N. Buchholz, William J. Pottorf, Conwin K. Vanterpool, Erik J. Behringer and Sue P. Duckles Chapter 23 All Your Eggs in One Basket: Mechanisms of Xenobiotic Induced Female Reproductive Senescence 559 Alexander P. Sobinoff, Ilana R. Bernstein and Eileen A. McLaughlin Part 3 Human 585 Chapter 24 Parkinson’s Disease: Insights from the Laboratory and Clinical Therapeutics 587 Jing-ye Zhou, Yong Yu, Xian-Lun Zhu, Chi-Ping Ng, Gang Lu and Wai-Sang Poon Chapter 25 The Emerging Role of Centromere/Kinetochore Proteins in Cellular Senescence 617 Kayoko Maehara Chapter 26 The Functioning of “Aged” Heterochromatin 631 Teimuraz A. Lezhava, Tinatin A. Jokhadze and Jamlet R. Monaselidze Chapter 27 New Targets for the Identification of an Anti-Inflammatory Anti-Senescence Activity 647 Patrizia d’Alessio, Annelise Bennaceur-Griscelli, Rita Ostan and Claudio Franceschi Chapter 28 Molecular Biomarkers of Aging 667 Sergio Davinelli, Sonya Vasto, Calogero Caruso, Davide Zella and Giovanni Scapagnini Chapter 29 Female Vascular Senescence 681 Susana Novella, Ana Paula Dantas, Gloria Segarra, Carlos Hermenegildo and Pascual Medina XII Contents Chapter 30 Pharmacologic Inhibition of Cardiac Stem Cell Senescence 705 Daniela Cesselli, Angela Caragnano, Natascha Bergamin, Veronica Zanon, Nicoletta Finato, Ugolino Livi, Carlo Alberto Beltrami and Antonio Paolo Beltrami Chapter 31 Central Immune Senescence, Reversal Potentials 735 Krisztian Kvell and Judit E. Pongracz Chapter 32 Age-Related Changes in Human Skin by Confocal Laser Scanning Microscope 757 Karine Cucumel, Jean Marie Botto, Nouha Domloge and Claude Dal Farra Chapter 33 Imagistic Noninvasive Assessment of Skin Ageing and Anti-Ageing Therapies 773 Maria Crisan, Radu Badea, Carlo Cattani and Diana Crisan Chapter 34 The Level of ROS and DNA Damage Mediate with the Type of Cell Death, Senescence or Apoptosis 797 Takafumi Inoue and Norio Wake Chapter 35 Reviewing the Life Cycle: Women’s Lives in the Light of Social Changes 807 Anna Freixas, Bárbara Luque and Amalia Reina Chapter 36 Multi-Purpose Activities in Ergotherapy 831 Hulya Yucel Preface This book is aimed to describe all the phenomena related to aging and senescence of all forms of life on Earth, i.e. plants, animals and the human beings. The book is comprised of 36 chapters written by diverse authors, including botanists, zoologists and physicians who study the aging and senescence of plants, animals and humans from structural and functional viewpoints. Aging is the time frame during which a person, animal or a plant has lived, or a thing has existed. On the contrary, senescence are the signs of old age that a person, animal or a plant shows once they get old. This book aims to describe all the phenomena appearing in plants, animals and humans after they got old and became senescent. The book contains 36 carefully reviewed chapters written by different authors, aiming to describe the aging and senescent changes of living creatures, i.e. plants and animals. In each section, the chapters are arranged from lower plants or animals to higher creatures, as well as from the organ of movement to cardiovascular, visceral and neuro-sensory systems, according to the order of anatomy and histology. Thus, the readers will be able to carry each volume easily. The Editor hopes that this book will have an interactive role in various fields of biology and medicine necessary to conduct further studies on aging and senescence. It should recount the background and current status of our knowledge in this field as well. Finally, the Editor would like to express sincere gratitude to all the contributing authors and the staff of InTech – Open Access Publisher, especially Ms. Iva Simcic who regularly communicated with the editor and the respective authors, for their expertise and cooperation in the publication of this book. Dr. Tetsuji Nagata Shinshu University School of Medicine Japan Part 1 Plant Chapter 1 Photo- and Free Radical-Mediated Oxidation of Lipid Components During the Senescence of Phototrophic Organisms Jean-François Rontani Laboratory of Microbiology, Geochemistry and Marine Ecology (UMR 6117), Center of Oceanology of Marseille, Aix-Marseille University, Campus of Luminy, Marseille, France 1. Introduction Recently, the role played by photochemical and free radical-mediated processes in the degradation of lipid components during the senescence of phototrophic organisms was investigated. The present paper reviews the results obtained in the course of these studies. In a first part, visible and UV light-induced photooxidation of the main lipid cell components (chlorophylls, carotenoids, sterols, unsaturated fatty acids, highly branched isoprenoid and linear alkenes, alkenones, cuticular waxes ...) in senescent phototrophic organisms (phytoplankton, cyanobacteria, higher plants, purple sulfur bacteria and aerobic anoxygenic phototrophic bacteria) is examined. Probably due to its long lifetime in hydrophobic micro-environments and thus in senescent cells, singlet oxygen plays a key role in the photodegradation of most of the lipid components. The second part of this paper describes the free radical oxidation (autoxidation) of lipid components during the senescence of phototrophic organisms, which have been virtually ignored until now in the literature. In senescent phototrophic organisms , the mechanism of initiation of free-radical oxidation seems to be the homolytic cleavage (catalyzed by some metal ions) of photochemically produced hydroperoxides. It was also demonstrated recently that viral infection and autocatalytic programmed cell death could also lead to elevated production of reactive oxygen species (ROS) able to induce the degradation of cell components. 2. Photodegradation processes in phototrophic organisms Several works suggested photo-oxidation as an important sink of organic matter in the photic layer of oceans (Zafiriou, 1977; Zafiriou et al., 1984). However, due to the lack of suitable markers this phenomenon has never been fully addressed. Owing to the problem of stratospheric ozone depletion, some studies have recently examined the degradative effects of enhanced UV-B doses on phytoplanktonic lipids (He and Häder, 2002). However, photochemical damages in phytoplanktonic cells are not a monopoly of UV radiation. In fact, due to the presence of chlorophylls (which are very efficient photosensitizers (Foote, 1976; Knox and Dodge, 1985)), numerous organic components of phytoplankton are susceptible to being photodegraded during senescence by photosynthetically active radiation (PAR). Senescence 4 2.1 Photodegradation of the main lipidic components of phytoplankton during senescence When a chlorophyll molecule absorbs a quantum of light energy, an excited singlet state ( 1 Chl) is formed which, in healthy cells, leads predominantly to the characteristic fast reactions of photosynthesis (Foote, 1976). However, a small proportion (<0.1%) undergoes intersystem crossing (ISC) to form the longer lived triplet state ( 3Chl; Knox and Dodge, 1985). 3 Chl is not only itself potentially damaging in type I reactions (hydrogen atom or electron abstraction) (Knox and Dodge, 1985), but can also generate highly reactive oxygen species (ROS) and, in particular, singlet oxygen ( 1 O 2 ), by reaction with ground state oxygen ( 3 O 2 ) via Type II processes. In order to avoid oxidative damage, there are many antioxidant protective mechanisms in chloroplasts. Carotenoids quench 3 Chl and 1 O 2 by energy transfer mechanisms at very high rates (Foote, 1976) and tocopherols can remove 1 O 2 , O 2 - , HOO and HO by acting as sacrificial scavengers (Halliwell, 1987). Superoxide dismutase enzyme (SOD) and ascorbic acid may also scavenge O 2 - (Halliwell, 1987), while catalase activity decreases H 2 O 2 levels. In senescent phototrophic organisms, the fast reactions of photosynthesis clearly do not operate, so an accelerated rate of formation of 3Chl and 1 O 2 would be expected (Nelson, 1993). The rate of formation of these potentially damaging species can then exceed the quenching capacity of the photoprotective system and photodegradation can occur (photodynamic effect; Merzlyak and Hendry, 1994). In phytodetritus, when the ordered structure of the thylakoid membranes has been disrupted, pigments tend to remain associated with other hydrophobic cellular components such as membrane lipids (Nelson, 1993). As a result, the photooxidative effect of chlorophyll sensitization might be strongly amplified within such a hydrophobic micro-environment. Moreover, the lifetime of 1 O 2 produced from sensitizers in a lipid-rich hydrophobic environment could be longer, and its potential diffusive distance greater, than its behaviour in aqueous solution (Suwa et al., 1977). It is not surprising, therefore, that photodegradation processes act on the majority of unsaturated lipid components of senescent phytoplankton. 2.1.1 Chlorophylls Irradiation of dead phytoplankton cells by PAR and UVR radiations results in rapid degradation of chlorophylls (Nelson, 1993; Rontani et al., 1995; Christodoulou et al., 2010). Photodegradation of chlorophyll- a and - c in killed cells of E. huxleyi appeared to be induced by both PAR and UVR (Christodoulou et al., 2010). The photochemical degradation of chlorophylls has so far been studied almost exclusively with respect to the macrocycle moiety of the molecule, which is the more reactive. Despite some progress regarding intermediary photoproducts (Engel et al., 1991; Iturraspe et al., 1994), no stable and specific markers for the chlorophyll macrocycle photodegradation have been characterised. The isoprenoid phytyl side-chain of chlorophylls is also sensitive to photochemical processes. In fact, in phytodetritus, the photodegradation rates were only 3 to 5 times higher for the chlorophyll tetrapyrrolic structure than for the phytyl side-chain (Cuny et al., 1999; Christodoulou et al., 2010). Analysis of isoprenoid photoproducts of chlorophylls after irradiation of different dead phytoplanktonic cells by visible light clearly established that the photodegradation of the chlorophyll phytyl side-chain in phytodetritus involved mainly Photo- and Free Radical-Mediated Oxidation of Lipid Components During the Senescence of Phototrophic Organisms 5 1 O 2. The type II (i.e. involving 1 O 2 ) photosensitized oxidation of the phytol moiety of chlorophylls leads to the production of photoproducts of structures a and b (Fig. 1), quantifiable after NaBH 4 -reduction and alkaline hydrolysis respectively in the form of 6,10,14-trimethylpentadecan-2-one ( 1 ) (phytone) and 3-methylidene-7,11,15-trimethyl- hexadecan-1,2-diol (phytyldiol) ( 2 ) (Fig. 1) (Rontani et al., 1994). R CH 2 OR' R CH 2 OR' R CH 2 OH R R CHO R O OOH OH OOH OR' R OH OR' OH R CH 2 OR' OH Alkaline hydrolysis Alkaline hydrolysis a b Retroaldol R = R' = R" = More or less oxidized tetrapyrrolic structure C (CH 2 ) 2 O R" R CH 2 OR' PAR UVR Photosensitized isomerization UVR NaBH 4 reduction NaBH 4 reduction Type II photosensitized degradation R CH 2 OR' R CH 2 OH OOH OH R CH 2 OR' OH Alkaline hydrolysis c NaBH 4 reduction Type II photosensitized degradation PAR UVR Type II photosensitized degradation PAR UVR 1 2 3 and 4 Fig. 1. Photooxidation of chlorophyll phytyl side-chain and reactions of oxidation products during alkaline hydrolysis. Senescence 6 Irradiation with UVR resulted in the additional production of small amounts of Z -phytol and Z and E -3,7,11,15-tetramethylhexadec-3-en-1,2-diols ( 3,4 ) (Christodoulou et al., 2010). The detection of Z -phytol allowed to demonstrate the induction of cis-trans photosensitized isomerization by UVR. These reactions probably involve triplet states of ketones as sensitizers. Type II photosensitized oxidation of the Z configuration of phytol, which should lead to the production of photoproducts of structures a , b and c (Fig. 1) (Schulte-Elte et al., 1979), explains the detection of small amounts of Z and E -3,7,11,15-tetramethylhexadec-3-en- 1,2-diols ( 3,4 ) after irradiation with UVR. Irradiation with UVR also resulted in a faster degradation of chlorophyll phytyl side-chain oxidation products (Christodoulou et al., 2010). This higher reactivity was attributed to UVR-induced homolysis of the peroxyl group of photoproducts of structures a , b and c (Fig. 1). Phytyldiol ( 2 ) is ubiquitous in the marine environment and has been proposed as tracer for photodegradation of chlorophyll’s phytyl side chain (Rontani et al. 1994; 1996a; Cuny and Rontani 1999). Further, the molar ratio phytyldiol:phytol (Chlorophyll Phytyl side-chain Photodegradation Index, CPPI) was employed to estimate the extent of chlorophyll photodegraded in natural marine samples by the empirical equation: chlorophyll photodegradation % = (1-(CPPI + 1) -18.5 ) x 100 (Cuny et al. 2002). 2.1.2 Carotenoids In phytodetritus, chlorophylls and carotenoids remain in a close molecular-scale association at relatively high localized concentrations, even though the structure of the thylakoid membrane has been disrupted (Nelson, 1993). Thus, the sensitized photooxidation of carotenoids is enhanced. The photosensitized oxidation (involving 1 O 2) of carotenoids in solvents has been studied (Iseo et al., 1972) and loliolide ( 5 ), iso -loliolide ( 6 ) and dihydroactinidiolide ( 7 ) (Fig. 2) were identified as major photoproducts, depending on the functionality of carotenoids at C-3. Loliolide ( 5 ) and iso -loliolide ( 6 ) have been detected in killed cells of Dunaliella sp. irradiated by visible light (Rontani et al., 1998). However, due to their apparent production by anaerobic bacteria (Repeta, 1989) and during dark incubations of killed phytoplanktonic cells (Rontani et al., 1998), these compounds cannot constitute unequivocal indicators of photooxidative processes. O O O HO HO O O O 5 6 7 1 2 3 Fig. 2. Structure of the main carotenoid oxidation products. 2.1.3 5 -sterols As important unsaturated components of biological membranes, 5 -sterols are highly susceptible to photooxidative degradation during the senescence of phytoplankton. Irradiation by visible light of killed cells of Skeletonema costatum , Dunaliella sp.,