Advances in Geroscience

Felipe Sierra • Ronald KohanskiEditors

Advances in Geroscience

ISBN 978-3-319-23245-4 ISBN 978-3-319-23246-1 (eBook)DOI 10.1007/978-3-319-23246-1

Library of Congress Control Number: 2015955267

Springer Cham Heidelberg New York Dordrecht London© Springer International Publishing 2016This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part ofthe material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,broadcasting, reproduction on microfilms or in any other physical way, and transmission or informationstorage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodologynow known or hereafter developed.The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoes not imply, even in the absence of a specific statement, that such names are exempt from the relevantprotective laws and regulations and therefore free for general use.The publisher, the authors and the editors are safe to assume that the advice and information in this bookare believed to be true and accurate at the date of publication. Neither the publisher nor the authors or theeditors give a warranty, express or implied, with respect to the material contained herein or for any errorsor omissions that may have been made.

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EditorsFelipe SierraDivision of Aging BiologyNational Institutes of Health/NationalInstitute of AgingBethesda, MDUSA

Ronald KohanskiDivision of Aging BiologyNational Institutes of Health/NationalInstitute of AgingBethesda, MDUSA

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Foreword

In an introduction to a 2003 special issue of Science [1], my colleagues and Iemphasized that “We have focused on physiological mechanisms underlying pro-cesses of aging, rather than on the large array of debilitating and costly disordersthat so commonly emerge during the latter half of the life-spans of human beings.”That was before the days of Geroscience, however! But what exactly is Geroscience? It is a term coined by my colleague and friend, Gordon Lithgow, a professor at theBuck Institute for Research on Aging who, true to his Scottish heritage, is thriftywith the use of all instruments of commerce, including terminology. Gordon usedthat nomenclature to summarize a new interdisciplinary research enterprise at theBuck Center; although it needs some grammatical editing, it is quite informative:“We consider that the relationship between aging and age-related disease (is) animportant problem that can be tackled through an interdisciplinary approach”(http://www.geroscienceonline.org/index.php). This view emphasizes the conceptthat it is not only difficult to disassociate fundamental processes of aging from thenumerous diseases of aging, but that joint investigations of these two domains ofscholarship are essential if we are to unravel the pathogenesis of atherosclerosis,myocardial infarctions, strokes, non-ischemic heart failure, benign and malignantneoplasms, dementias of the Alzheimer type, frontal temporal dementias,Parkinson’s disease and Lewy body dementias, peripheral neuropathies, cataractsand age-related macular degeneration, presbycusis, chronic obstructive pulmonarydisease, type 2 diabetes mellitus, the metabolic syndrome, osteoporosis, osteoarthri-tis, sarcopenia, glomerulosclerosis, etc.

The editors of this volume, Felipe Sierra and Ronald Kohanski, have takenthis concept to an exciting new level of implementation. As the Director of theDivision of Aging Biology of the National Institute on Aging, Felipe approachedhis counterparts at more than twenty sister NIH institutes with narrow interestsin specific diseases of aging with the following paraphrased sales pitch: “Let’shave a discussion about how basic processes of aging are the major risk factor foryour disease X. But first, I want to assure you that I do not want your money formy own institute! I want to start a ‘Geroscience Interest Group’ so that we canwork together to accelerate progress towards the enhancement of healthy human

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aging.” The response was overwhelmingly enthusiastic and resulted in a seriesof productive joint conferences, including a 2013 Summit meeting at the NIH[2]. Readers are urged to learn more about this trans-NIH initiative via Felipe’sexcellent video on the subject: http://www.nia.nih.gov/about/links/2013/07/video-dr-felipe-sierra-discusses-trans-nih-geroscience-interest-group-and-more.

This volume, despite its 19 chapters and its stellar list of authors, can best beviewed as just a beginning step for Geroscience. Given the extent of research fund-ing that it richly deserves – far more than the current NIH pay lines – we can antici-pate major basic and translational advances in our healthspans, at which point wecan go to the Food and Drug Administration and point out that the side effect of ourresearch – increased longevity – can really be a good thing for humanity. As the lateCharlie Chaplin pointed out, “we are all amateurs; we don’t live long enough tobecome anything else” [1].

Seattle, WA, USA George M. Martin, M.D.June 5, 2015

References

1. Martin GM, LaMarco K, Strauss E, L Kelner K (2003) Research on aging: the end of the begin-ning. Science 28;299(5611):1339–1341

2. Burch JB, Augustine AD, Frieden LA, Hadley E, Howcroft TK, Johnson R, Khalsa PS, KohanskiRA, Li XL, Macchiarini F, Niederehe G, Oh YS, Pawlyk AC, Rodriguez H, Rowland JH, ShenGL, Sierra F, Wise BC (2014) Advances in geroscience: impact on healthspan and chronicdisease. J Gerontol A Biol Sci Med Sci 69(Suppl 1):S1–S3

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Preface

Geroscience is a new field that aims to bridge two communities: biologists focusedon understanding the basic mechanisms that drive aging, and geriatricians attempt-ing to improve the quality of life of elderly patients. Geroscience has been defined(Wikipedia) as “an interdisciplinary field that aims to understand the relationshipbetween aging and age-related diseases.” Because aging is the major risk factor formost chronic diseases, the “Geroscience Hypothesis” posits that common biologicalmechanisms of aging play important roles in the susceptibility of aged individualsto multiple chronic diseases.

The role of aging as a driver of chronic diseases is often downplayed under theassumption that aging is a non-modifiable risk factor. Yet we know that the rate ofaging (however that is defined, as decay in function or susceptibility to disease) ismodifiable by simple changes in the environment: a healthy diet, moderate exercise,and other elements of a generally healthy lifestyle will increase a person’s chancesof leading a longer and healthier life. In fact it is a dietary intervention, diet restric-tion, that provided the first handle to biologists’ intent to understand the underpin-nings of the aging process. That work, coupled with genetic experiments inshort-lived simple organisms ranging from yeast to flies and worms, allowed scien-tists to unravel some of the major mechanisms involved. Furthermore, driven pri-marily by the Intervention Testing Program (created and supported by the NationalInstitute on Aging), the field has moved recently to defining pharmacological inter-ventions that expand lifespan in rodents (mainly mice). In addition to these impres-sive advances in terms of increasing lifespan, recently there has been a shift infocus, towards measuring healthspan as well as lifespan. Indeed, while some inter-ventions (such as resveratrol) only increase health but not lifespan in mice, a hand-ful of other interventions have been shown to increase both, although with the strongcaveat that no manipulation has achieved that goal without having some secondarynegative effects.

The enormous aging of the population worldwide, with the oldest-old being theage segment with the fastest growth, poses an urgent dilemma: if aging is indeed thelargest risk factor for most chronic diseases, this increase in the proportion of elderlywill necessarily pose an insurmountable challenge to the world’s economic and

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health-care systems. Fortunately, at the same time that this demographic change isreaching a critical stage, our understanding of aging biology is allowing scientists toconsider the possibility of intervening to delay aging, and hopefully, with it allmajor chronic diseases. This improved knowledge has allowed the organization ofconcepts into six to eight hallmarks or pillars, believed to be the main drivers of theprocess. While some details still need further clarification, there is broad agreementwithin the research community about these major drivers, and differences onlyreflect different biases and granularity.

These advances and the emerging opportunity to modify the process of aging bypharmacological means spawned the appearance of the new field of Geroscience.The initial concept came from a group at the Buck Institute for Research on Agingwhich, under the leadership of Dr. Gordon Lithgow, put forward a successful pro-posal to the Common Fund of the National Institute of Health. This project,Interdisciplinary Research Consortium on Geroscience, was funded for 5 yearsbetween 2007 and 2012. Subsequent to that effort, the editors of this book started atrans-NIH effort following the same line of thinking and resulting in the formationof the trans-NIH GeroScience Interest Group (GSIG). The effort attracted the atten-tion of over 20 different institutes within the NIH, as well as wide support from boththe scientific community and, importantly, non-federal advocacy and supportgroups. With the imprimatur of so many NIH institutes, the subsequent growth ofthe field was impressive and culminated in the organization of a large Summit,Advances in Geroscience: Impact on Healthspan and Chronic Disease, held in theNIH Campus on October/November 2013. In turn, that effort resulted in the publi-cation of a White Paper in November 2014 in the Journal Cell.

For whom is the book written? Geroscience is an interdisciplinary field attempt-ing to address the mechanisms by which aging biology is the main risk factor forchronic diseases. As such, this book examines those mechanisms and it provides anemerging overview of the new discipline of Geroscience. Each chapter aims at con-necting the clinical manifestation of specific age-related chronic diseases with themajor pillars of aging biology. These pillars are suspected (or in some cases, known)to play a role in the etiology of these diseases, not just singly but in multiple dis-eases because aging is the major risk factor for their appearance. As such, eachchapter combines features of clinical science and basic biology, and it is hoped thatthis approach will be informative and enlightening to both these communities: phy-sicians will hopefully learn about the basic underpinnings of aging that might affectthe outcome of chronic diseases and/or treatments, while basic scientists mightprofit from learning about clinical aspects of their disease of interest in the contextof aging. Altogether, the editors and authors anticipate that this book will raise fur-ther awareness of the molecular mechanisms which might become targets for fur-ther investigation and, ultimately, new targets to combat multiple comorbidities atonce.

This book examines the biological mechanisms and clinical consequences ofaging by providing specific coverage on a wide range of chronic diseases, fromarthritis and cancer to dementia and stroke among others. This book begins with anintroduction of the general principles, including both a description of current

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thinking in aging biology and a description of the Geroscience Hypothesis, withsome background on the critical role that epidemiology has played in defining ourbasic understanding of age-related chronic diseases. Each of the following 16 chap-ters focuses on one particular disease, or group of related diseases, with an emphasison how aging is a risk factor. This book finishes with a global discussion of pain inthe elderly and a commentary on the important topic of translation into the clinicand the necessity of cross-fertilization between clinicians and basic scientists.Unfortunately, not all diseases afflicting the elderly have been covered, and thisomission is simply the result of space limitations. It is hoped that this book willentice experts in those areas to think more deeply about the basis on which aging asa risk factor for their specialty disease, and perhaps publish their thoughts on thissubject.

Contributors to this volume represent a large range of disciplines. An effort wasmade, whenever possible and appropriate, to engage in each chapter both basicscientists and clinicians; the editors are enormously thankful to all authors for theeffort and sense of shared responsibility. Importantly, the editors thank all membersof the GSIG executive committee for their support during the preparation of thisbook and the help provided on the selection of authors. Similarly, GSIG membersare to be commended for the additional editorial work to complete this volume.

The editors believe that this book presents vital information and ideas that canhelp readers better understand how aging is a critical – but malleable – risk factor inchronic diseases of the elderly. The potential to alter the rate of aging is at the heartof Geroscience, and achieving that goal should improve lifespan and healthspan inthe human population.

Bethesda, MD, USA Felipe SierraRonald A. Kohanski

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The Geroscience Hypothesis: Is It Possible to Change the Rate of Aging? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1Steven N. Austad

Etiological Role of Aging in Chronic Diseases: From Epidemiological Evidence to the New Geroscience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37Linda P. Fried and Luigi Ferrucci

The Impact of Aging on Cancer Progression and Treatment . . . . . . . . . . . . 53Shenghui He and Norman E. Sharpless

The Impact of Cancer Treatments on Aging . . . . . . . . . . . . . . . . . . . . . . . . . 85Changhan Lee and Valter Longo

Cardiovascular Disease and Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121Ying Ann Chiao, Edward Lakatta, Zoltan Ungvari, Dao-Fu Dai, and Peter Rabinovitch

The Impact of Aging on Ischemic Stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . 161Farida Sohrabji

The Role of Aging in Alzheimer’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . 197Geoffrey A. Kerchner and Tony Wyss-Coray

Parkinson’s Disease and Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229Julie K. Andersen and Shankar Chinta

Aging and the Bone-Muscle Interface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257Simon Melov and Clifford J. Rosen

Osteoporosis and Mechanisms of Skeletal Aging . . . . . . . . . . . . . . . . . . . . . 277Julie Glowacki and Tamara Vokes

Osteoarthritis in the Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309Richard F. Loeser and Martin Lotz

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Diabetes and Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355Nicolas Musi and Andrzej Bartke

Renal Aging and Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377John P. Higgins and Stuart K. Kim

Asthma and Aging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397Nicola A. Hanania and Paula Busse

Aging in COPD and Idiopathic Pulmonary Fibrosis . . . . . . . . . . . . . . . . . . 429Cecilia G. Sanchez

Age-Related Macular Degeneration and Vision Impairment . . . . . . . . . . . 471Charles Wright and Jayakrishna Ambati

HIV and Aging: Parallels and Synergistic Mechanisms Leading to Premature Disease and Functional Decline . . . . . . . . . . . . . . . . . . . . . . . 509Anna Hearps, Katherine Schafer, Kevin High, and Alan Landay

Pain in the Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551Roger B. Fillingim, Dennis C. Turk, and Robert P. Yezierski

The Way Forward: Translation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 593James L. Kirkland and Tamar Tchkonia

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Contributors

Jayakrishna Ambati Department of Ophthalmology and Visual Sciences,University of Kentucky, Lexington, KY, USA

Julie K. Andersen, Ph.D. Buck Institute for Research on Aging, Novato, CA,USA

Steven N. Austad, Ph.D. Department of Biology, University of Alabamaat Birmingham, Birmingham, UK

Andrzej Bartke, Ph.D. Department of Medicine, Southern Illinois UniversitySchool of Medicine, Springfield, IL, USA

Paula Busse, M.D. Department of Medicine, Icahn School of Medicine, Mount Sinai, NY, USA

Ying Ann Chiao, Ph.D. Department of Pathology, University of Washington,Seattle, WA, USA

Shankar Chinta, Ph.D. Buck Institute for Research on Aging, Novato, CA, USA

Dao-Fu Dai, M.D., Ph.D. Department of Pathology, University of Washington,Seattle, WA, USA

Luigi Ferrucci Intramural Research Program, National Institute on Aging,Bethesda, MD, USA

Roger B. Fillingim, Ph.D. Pain Research and Intervention Center of Excellence,University of Florida, Gainesville, FL, USA

Linda P. Fried Mailman School of Public Health, Columbia University MedicalCenter, New York, NY, USA

Julie Glowacki, Ph.D. Department of Orthopedic Surgery, Brigham andWomen’s Hospital, Boston, MA, USA

Nicola A. Hanania, M.D., M.S. Department of Medicine, Baylor Collegeof Medicine, Houston, TX, USA

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Shenghui He, Ph.D. Department of Genetics, The Lineberger ComprehensiveCancer Center, University of North Carolina School Medicine, CB #7295, Chapel Hill, NC, USA

Anna Hearps, Ph.D. Centre for Biomedical Research, Burnet Institute,Melbourne, VIC, Australia

John P. Higgins, M.D. Department Pathology, Stanford University MedicalCenter, Stanford, CA, USA

Kevin High, M.D. Department of Internal Medicine, Section on InfectiousDiseases, Wake Forest School of Medicine, Winston-Salem, NC, USA

Geoffrey A. Kerchner Department of Neurology and Neurological Sciences,Stanford University School of Medicine, Stanford, CA, USA

Stuart K. Kim, Ph.D. Department Developmental Biology and Genetics,Stanford University Medical Center, Stanford, CA, USA

James L. Kirkland, M.D., Ph.D. Aging Research, Robert and Arlene KogodCenter on Aging, Mayo Clinic, Rochester, MN, USA

Edward Lakatta, M.D. Laboratory of Cardiovascular Science, BiomedicalResearch Center, National Institute of Aging, Baltimore, USA

Alan Landay, Ph.D. Department of Immunology/Microbiology, Rush UniversityMedical Center, Chicago, IL, USA

Changhan Lee, Ph.D. Davis School of Gerontology, University of SouthernCalifornia, Los Angeles, CA, USA

Richard F. Loeser, M.D. Division of Rheumatology, Allergy, and Immunology,Thurston Arthritis Research Center, University of North Carolina School ofMedicine, Chapel Hill, NC, USA

Valter Longo, Ph.D. Davis School of Gerontology, University of SouthernCalifornia, Los Angeles, CA, USA

IFOM, FIRC Institute of Molecular Oncology, Milan, Italy

Martin Lotz, M.D. Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA

Simon Melov, Ph.D. Buck Institute for Research on Aging, Novato, CA, USA

Nicolas Musi, M.D. Department of Medicine, Sam and Ann Barshop Institute for Longevity and Aging Studies, San Antonio Geriatric Research, Education and Clinical Center, University of Texas Health Science Center, San Antonio, TX, USA

Peter Rabinovitch, M.D., Ph.D. Department of Pathology, Universityof Washington, Seattle, WA, USA

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Clifford J. Rosen, M.D. Department of Medicine, Musculoskeletal Center,Center for Clinical & Translational Research, Maine Medical Center ResearchInstitute, Scarborough, ME, USA

Cecilia G. Sanchez, Ph.D. Section of Pulmonary Diseases, Critical Careand Environmental Medicine, Tulane University Medical School, New Orleans, LA, USA

Katherine Schafer, M.D. Department of Internal Medicine, Section on InfectiousDiseases, Wake Forest School of Medicine, Winston-Salem, NC, USA

Norman E. Sharpless, M.D. Department of Genetics, The LinebergerComprehensive Cancer Center, University of North Carolina School Medicine,Chapel Hill, NC, USA

Farida Sohrabji, Ph.D. Texas A&M Health Science Center, Bryan, TX, USA

Tamar Tchkonia, Ph.D. Department of Medicine, Robert and Arlene KogodCenter on Aging, Mayo Clinic, Rochester, MN, USA

Dennis C. Turk, Ph.D. Department of Anesthesiology and Pain Medicine,University of Washington, Seattle, WA, USA

Zoltan Ungvari, M.D., Ph.D. Department of Geriatric Medicine, ReynoldsOklahoma Center on Aging, University of Oklahoma Health Science Center,Oklahoma City, OK, USA

Tamara Vokes, M.D. Department of Medicine, Section of Endocrinology,University of Chicago, Chicago, IL, USA

Charles Wright Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY, USA

Tony Wyss-Coray Department of Neurology and Neurological Sciences,Stanford University School of Medicine, Stanford, CA, USA

Center for Tissue Regeneration, Repair and Restoration, Veterans Affairs PaloAlto Health Care System, Palo Alto, CA, USA

Robert P. Yezierski, Ph.D. Pain Research and Intervention Center of Excellence,University of Florida, Gainesville, FL, USA

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Abbreviations

AAV Adeno-associated virusAβ Amyloid betaACEi Angiotensin converting enzyme inhibitorACL Anterior cruciate ligamentACOS Asthma-COPD overlap syndromeACT Asthma control testAD Alzheimer’s diseaseADCC Antibody-dependent cellular cytotoxicityADE Adverse drug eventsAF Atrial fibrillationAGE Advanced glycation end productAHR Airway hyperresponsivenessAIDS Acquired immunodeficiency syndromeAKT Protein kinase BAMD Age-related macular degenerationAMPK Adenine monophosphate-activated protein kinaseANI Asymptomatic neurocognitive impairmentAPP Amyloid precursor proteinARB Angiotensin 2 receptor blockerART Anti-retroviral therapyATP Adenosine-5’-triphosphateBALF Bronchoalveolar lavage fluidBBB Blood brain barrierBDNF Brain-derived neurotrophic factorBER Base excision repairBMD Bone mineral densityBMI Body mass indexBMP Bone morphogenetic proteinBMSC/B-MSC Bone marrow-derived stem cellBMU Basic multicellular unitBreg Regulatory B cells

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BV/TV Bone volume fractionCAC Coronary artery calciumCBT Cognitive behavior therapyCCI Chronic constriction injuryCD Cluster of differentiationCDC Center for Disease Control and PreventionCDK Cyclin-dependent kinaseCEE Conjugated equine estrogensCFA Complete Freund’s adjuvantCFB Complement factor BCGRP Calcitonin gene-related peptideCHF Congestive heart failureCLBP Chronic low back painCM Conditioned mediumCMV CytomegalovirusCNS Central nervous systemCNV Choroidal neovascularizationCOLD Chronic obstructive lung diseaseCOMP Cartilage oligomeric proteinCOMT Catechol-O-methyl transferaseCOPD Chronic obstructive pulmonary diseaseCOX2 Cyclooxygenase-2CPM Conditioned pain modulationCR Caloric restrictionCRP C-reactive proteinCSE Cigarette smoke extractCT Computed tomographyCTGF Connective tissue growth factorCVD Cardiovascular diseaseDA DopamineDAergic DopaminergicDBP Diastolic blood pressureDBS Deep brain stimulationDC Dendritic cellDDI Drug-drug interactionsDG Dentate gyrusDHEA DehydroepiandrosteroneDLB Dementia with Lewy bodiesDLCO Carbon monoxide diffusing capacityDMM Destabilized medial meniscusDPP Diabetes prevention programDR Dietary restrictionDRG Dorsal root gangliaDSB Double strand breakDSR Differential stress resistance

Abbreviations

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dsRNA Double-stranded RNADSS Differential stress sensitizationDXA Dual energy X-ray absorptiometryE2 EstradiolEa/Aa Ratio of early to late diastolic mitral annular velocityEBV Epstein-Barr virusECM Extracellular matrixEF Ejection fractionEF EnhanceFitnessEMT Epithelial-mesenchymal transitionEPC Endothelial progenitor celleQTL Expression quantitative trait lociER Endoplasmic reticulumERK Extracellular-regulated kinaseETC Electron transport chainEWAS Epigenome-wide association studyFDA Food and Drug AdministrationFFA Free fatty acidFGF Fibroblast growth factorFGFR2 Fibroblast growth factor receptor 2FIRKO Fat tissue-specific insulin receptor knockoutFOXO Forkhead box protein OFRP Frailty-related phenotypeFS Fractional shorteningFTIRM Fourier transformed infrared microepectroscopyGA Geographic atrophyGAD Glutamic acid decarboxylaseGALT Gut-associated lymphoid tissueGDF-11 Growth and differentiation factor 11GDNF Glial-derived neurotrophic factorGERD Gastroesophageal reflux diseaseGFAP Glial fibrillary acidic proteinGFP Green fluorescent proteinGH Growth hormoneGHR Growth hormone receptorGTT Glucose tolerance testGWAS Genome-wide association studyGzmB Granzyme BHAD HIV-associated dementiaHANA HIV-associated non-AIDSHAND HIV-associated neurocognitive disorderHAT Histone acetyl transferaseHCV Hepatitis C virusHDAC Histone deacetylaseHERV Human endogenous retroviruses

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HFD High-fat dietHIV Human immunodeficiency virusHLA Human leukocyte antigenHPA Hypothalamo-pituitary axisHPC Hematopoietic progenitor cellHPLC High pressure liquid chromatographyHPV Human papillomavirusHR Heart rateHSC Hematopoietic stem cellshsCRP High-sensitivity C-reactive proteinHSP Heat shock proteinHSV Herpes simplex virusHT Hormone therapyICH Intracerebral hemorrhageICS Inhaled corticosteroidsI-FABP Intestinal fatty acid binding proteinIFN InterferonIGF Insulin-like growth factorIGFBP IGF binding proteinIGT Insulin glucose tolerance testIL InterleukinIND Investigational new drugiNOS Inducible nitric oxide synthaseIOM Institute of MedicineIPF Idiopathic pulmonary fibrosisiPS/iPSC Induced pluripotent stem cellIR Ionizing radiationIRAP IL-1 receptor antagonist proteinIRS1 Insulin receptor substrate 1ISH Isolated systolic hypertensionITM Intima-media thicknessITP Interventions Testing ProgramKMT Lysine methyl transferaseLBP Low back painLBP LPS binding proteinLDL Low density lipoproteinL-DOPA Levo-DOPAlncRNA Long non-coding RNALOA Late onset asthmaLPS LipopolysaccharideLSA Long-standing asthmaLSD Lysine-specific demethylaseLV Left ventricleLVH Left ventricular hypertrophyMAC Membrane attack complex

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MAO-B Monoamine oxidase BMAP Mean arterial pressureMCAo Middle cerebral artery occlusionMCAT Mitochondrial-directed catalaseMD2 Myeloid differentiation factor 2MDP Mitochondrial-derived peptidesmiRNA/miR MicroRNAMMP Matrix metalloproteinaseMMSE Mini-mental status examMND Mild neurocognitive disordermPTP Mitochondrial permeability transition poreMRI Magnetic resonance imagingMRS Magnetic resonance spectroscopyMSC Marrow stromal cellMSC Mesenchymal stem cellmtDNA Mitochondrial DNAmTOR Mechanistic target of rapamycinmTORC1 mTOR complex 1mtROS Mitochondrial ROSNAD+ Nicotinamide adenine dinucleotideNADC Non-AIDS-defining cancersncRNA Non-coding RNANER Nucleotide excision repairNET Neutrophil extracellular trapNHEJ Non-homologous end joiningNIA National Institute on AgingNIH National Institutes of HealthNK cell Natural killer cellNLRP3 Nucleotide-binding domain and leucine-rich repeat pyrin domain

containing 3NMDA N-methyl-D-aspartateNO Nitric oxideNOX NAP(P)H oxidaseNPC Neural precursor/progenitor cellNrf2 Nuclear factor erythroid-derived 2NRTI Nucleos(t)ide reverse transcriptase inhibitorNSAID Nonsteroidal anti-inflammatory drugnvAMD Neovascular AMDOA OsteoarthritisOPG OsteoprotegerinOR Odds ratioORF Open reading framePAMP Pathogen-associated molecular patternPAWH People aging with HIVPBMC Peripheral blood mononuclear cell

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PD Parkinson’s diseasePD1 Programmed cell death protein 1PDGF Platelet-derived growth factorPEDF Pigmented epithelium-derived factorPET Positron emission tomographyPGC-1α PPAR-gamma coactivator 1-alphaPGE2 Prostaglandin E2PHB1 Prohibitin 1PI Protease inhibitorPI3K Phosphatidyl inositol 3 kinasePKA Protein kinase APKC Protein kinase CPMN Polymorphonuclear cellPolg DNA polymerase gammaPPARγ Peroxisome proliferator-activated receptor gammapQCT Peripheral quantitative computed tomographyPRR Pattern recognition receptorPSNL Partial sciatic nerve ligationPSVT Paroxysmal supraventricular tachycardiaPTEN Phosphatase and tensin homologPTH Parathyroid hormoneRAAS Renin-angiotensin-aldosterone systemRAGE Receptor for advanced glycation end productRANKL Receptor activator of nuclear factor kappa B ligandRAP Retinal angiomatous proliferationRAS Renin-angiotensin systemRB RetinoblastomaRCT Randomized control trialRI Recombinant inbredRNS Reactive nitrogen speciesROS Reactive oxygen speciesRPE Retinal pigmented epitheliumRSV Respiratory syncytial virusRT Reverse transcriptaseRTL Recombinant T cell receptor ligandSABA Short-acting b adrenergic 2 receptor agonistSA-βGal Senescence-associated beta galactosidaseSAHF Senescence-associated heterochromatic fociSAM Senescence-accelerated mouseSASP Senescence-associated secretory phenotypeSBP Systolic blood pressuresCD Soluble cluster of differentiationSD-OCT Spectral domain optical coherence tomographySERM Selected estrogen receptor modulatorSGZ Subgranular zone

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SHR Spontaneously hypertensive ratSIRT1 Sirtuin1SIV Simian immunodeficiency virusSNAE Serious non-AIDS eventsSNP Single nucleotide polymorphismSNpc Substantia nigra pars compactaSNS Sympathetic nervous systemSOD Superoxide dismutaseSPF Specific pathogen freeSPT Skin prick testingSRM Selected reaction monitoringSTAT Signal transducer and activator of transcriptionSVZ Subventricular zoneT TestosteroneT2DM Type 2 diabetes mellitusTB TuberculosisTC Tai ChiTCR T cell receptorTERT Telomerase reverse transcriptaseTGFβ Transforming growth factor betaTIA Transient ischemic attackTIMP Tissue inhibitor of matrix metalloproteinaseTLR Toll-like receptorTNFα Tumor necrosis factor alphaTNFR1 Tumor necrosis factor receptor 1tPA Tissue plasminogen activatorTreg Regulatory T cellsTSA Trichostatin AUPR Unfolded protein responseUPS Ubiquitin-proteasome systemUPS Unfolded protein stressVE Ventricular ectopyVEGF Vascular endothelial growth factorVEGFR VEGF receptorVFA Vertebral fracture assessmentWHI Women’s Health InitiativeWRN Werner’s

Abbreviations