Genetic and Epigenetic Modulation of Cell Functions Physical Exercise by Genetic and • Italia Di Liegro Epigenetic Modulation of Cell Functions by Physical Exercise Edited by Italia Di Liegro Printed Edition of the Special Issue Published in Genes www.mdpi.com/journal/genes Genetic and Epigenetic Modulation of Cell Functions by Physical Exercise Genetic and Epigenetic Modulation of Cell Functions by Physical Exercise Special Issue Editor Italia Di Liegro MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade Special Issue Editor Italia Di Liegro Universita degli Studi di Palermo, Department of Experimental Biomedicine and Clinical Neurosciences (BioNeC), Palermo, Italy Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal Genes (ISSN 2073-4425) in 2019 (available at: https://www.mdpi.com/journal/genes/special issues/ Genetics Epigenetics Cell Exercise). For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year, Article Number, Page Range. ISBN 978-3-03928-480-1 (Pbk) ISBN 978-3-03928-481-8 (PDF) c 2020 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND. Contents About the Special Issue Editor ...................................... vii Italia Di Liegro Genetic and Epigenetic Modulation of Cell Functions by Physical Exercise Reprinted from: Genes 2019, 10, 1043, doi:10.3390/genes10121043 .................. 1 Linda S. Pescatello, Paul Parducci, Jill Livingston and Beth A. Taylor A Systematically Assembled Signature of Genes to be Deep-Sequenced for Their Associations with the Blood Pressure Response to Exercise Reprinted from: Genes 2019, 10, 295, doi:10.3390/genes10040295 ................... 6 Femke M. Prins, M. Abdullah Said, Yordi J. van de Vegte, Niek Verweij, Hilde E. Groot and Pim van der Harst Genetically Determined Physical Activity and Its Association with Circulating Blood Cells Reprinted from: Genes 2019, 10, 908, doi:10.3390/genes10110908 ................... 19 Alexander Schenk, Christine Koliamitra, Claus Jurgen ¨ Bauer, Robert Schier, Michal R. Schweiger, Wilhelm Bloch and Philipp Zimmer Impact of Acute Aerobic Exercise on Genome-Wide DNA-Methylation in Natural Killer Cells—A Pilot Study Reprinted from: Genes 2019, 10, 380, doi:10.3390/genes10050380 ................... 33 Antonio Paoli, Laura Mancin, Antonino Bianco, Ewan Thomas, Jo˜ao Felipe Mota and Fabio Piccini Ketogenic Diet and Microbiota: Friends or Enemies? Reprinted from: Genes 2019, 10, 534, doi:10.3390/genes10070534 ................... 43 Yi-Ching Liaw, Yung-Po Liaw and Tsuo-Hung Lan Physical Activity Might Reduce the Adverse Impacts of the FTO Gene Variant rs3751812 on the Body Mass Index of Adults in Taiwan Reprinted from: Genes 2019, 10, 354, doi:10.3390/genes10050354 ................... 62 Yasser Nassef, Oswald Ndi Nfor, Kuan-Jung Lee, Ming-Chih Chou and Yung-Po Liaw Association between Aerobic Exercise and High-Density Lipoprotein Cholesterol Levels across Various Ranges of Body Mass Index and Waist-Hip Ratio and the Modulating Role of the Hepatic Lipase rs1800588 Variant Reprinted from: Genes 2019, 10, 440, doi:10.3390/genes10060440 ................... 71 Juan Del Coso, Victor Moreno, Jorge Guti´errez-Hell´ın, Gabriel Baltazar-Martins, Carlos Ru´ız-Moreno, Mill´an Aguilar-Navarro, Beatriz Lara and Alejandro Luc´ıa ACTN3 R577X Genotype and Exercise Phenotypes in Recreational Marathon Runners Reprinted from: Genes 2019, 10, 413, doi:10.3390/genes10060413 ................... 82 Isabel Espinosa-Salinas, Rocio de la Iglesia, Gonzalo Colmenarejo, Susana Molina, Guillermo Reglero, J. Alfredo Martinez, Viviana Loria-Kohen and Ana Ramirez de Molina GCKR rs780094 Polymorphism as A Genetic Variant Involved in Physical Exercise Reprinted from: Genes 2019, 10, 570, doi:10.3390/genes10080570 ................... 97 v ȱ £¢ ǰȱ £¢ȱ£¢ ǰȱȱ ǰȱȱǰȱ ¿£ȱtosiewicz,IwonaBonisławskaandMałgorzataZychowska˙ ChangesinSerumIronandLeukocytemRNALevelsofGenesInvolvedinIronMetabolismin AmateurMarathonRunners—EffectoftheRunningPace Reprinted from: Genes 2019, 10, 460, doi:10.3390/genes10060460 ...................109 Carlo Maria Di Liegro, Gabriella Schiera, Patrizia Proia and Italia Di Liegro Physical Activity and Brain Health Reprinted from: Genes 2019, 10, 720, doi:10.3390/genes10090720 ...................121 vi About the Special Issue Editor Italia Di Liegro get a Master Degree in Biology in 1975 at the University of Palermo, Italy, with a thesis on sea urchin chromatin proteins. In 1981 she began working as University Researcher at a project on chromatin organization in sea urchin embryos. Afterwards, she turned to the rat developing central nervous system (CNS). In 2000 she was appointed as Associated Professor in Biochemistry, and in 2005 as Full Professor in Biochemistry, at the University of Palermo, Faculty of Medicine and Surgery. The studies on rat CNS allowed demonstration that regulation of histone variant expression is mainly post-transcriptional and involves both specific and general RNA-binding factors. In particular, at least two cDNAs were cloned in Di Liegro’s laboratory which encoded novel proteins (CSD-C2/PIPPin and LPI), possibly involved in this regulation. In parallel, IDL was involved in setting and analyzing an in vitro model of blood-brain barrier (BBB). In the last few years, Di Liegro’s group demonstrated that both neurons and glial cells shed extracellular vesicles (EVs) that transport angiogenic factors, and is now involved with studies aimed at ascertaining the role of EVs in both physiological and pathological conditions. vii G C A T T A C G G C A T genes Editorial Genetic and Epigenetic Modulation of Cell Functions by Physical Exercise Italia Di Liegro Department of Biomedicine, Neurosciences and Advanced Diagnostics (Dipartimento di Biomedicina, Neuroscienze e Diagnostica avanzata) (Bi.N.D.), University of Palermo, 90128 Palermo, Italy; [email protected]; Tel.: +39-091-238-97415/446 Received: 12 December 2019; Accepted: 13 December 2019; Published: 16 December 2019 Abstract: Since ancient times, the importance of physical activity (PA) and of a wholesome diet for human health has been clearly recognized. However, only recently, it has been acknowledged that PA can reverse at least some of the unwanted effects of a sedentary lifestyle, contributing to the treatment of pathologies such as hypertension and diabetes, to the delay of aging and neurodegeneration, and even to the improvement of immunity and cognitive processes. At the same time, the cellular and molecular bases of these effects are beginning to be uncovered. The original research articles and reviews published in this Special Issue on “Genetic and Epigenetic Modulation of Cell Functions by Physical Exercise” focus on different aspects of the genetics and molecular biology of PA effects on health and, in addition, on the effects of different genotypes on the ability to perform PA. All authors have read and agreed to the published version of the manuscript. Keywords: physical activity; physical exercise; aerobic exercise; exercise and health 1. Introduction The importance of exercise for health had already been recognized by ancient physicians [1]: for example, Hippocrates (c460–c370 BC) underlined that: “eating alone will not keep a man well, he must also take exercise” [1–3]. Moreover, Hippocrates considered exercise like a medicine and was the first recorded physician to provide a detailed written exercise prescription [Tipton, 2014]. Similarly, Herophilus (c335–c280 BC.) believed that exercise and a healthy diet were fundamental for maintaining a healthy body and a healthy mind [4]. Over the centuries, this belief has been expressed and clarified in detail many times [1,5]. Only recently, however, we have been starting to understand the cellular and molecular bases of the detrimental effects on health of a sedentary lifestyle, as well as the reasons why physical activity (PA) can function as a medicine to counteract these effects. This Special Issue was destined to discuss how cell functions can be modulated at both the genetic and the epigenetic level by physical exercise. Some of the original papers also deal with the effects of gene variants on the ability to perform PA. 2. Effects of Physical Exercise on Cardiovascular Disease, Inflammation, and Immunity The fact of the matter is that PA can counteract the development of hypertension in a dose-dependent manner [6]. This finding is of high relevance when we consider that hypertension is a widespread disorder as well as the most common risk factor for cardiovascular disease (CVD), which, in turn, is one of the leading causes of death [7–9]. In spite of these clear correlations, however, only a few patients with hypertension actually exercise. As discussed in one of the reviews published in this Special Issue, the reasons for the lack of interest in PA of most patients are many; one of them, however, can be found in the genetically determined efficacy of exercise, as shown in a systematic review of studies