THE FUTURE OF HUMAN HEALTHSPAN

Demography, Evolution, Medicine, and Bioengineering

TASK GROUP SUMMARIES

Conference

Arnold and Mabel Beckman Center

Irvine, California

November 14-16, 2007

THE NATIONAL ACADEMIES PRESS

Washington, D.C.
www.nap.edu



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THE FUTURE OF HUMAN HEALTHSPAN Demography, Evolution, Medicine, and Bioengineering TA S K G R O U P S U M M A R I E S Conference Arnold and Mabel Beckman Center Irvine, California November 14-16, 2007

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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001 NOTICE: The task group summaries in this publication are based on task group dis- cussions during the National Academies Keck Futures Initiative Conference The Future of Human Healthspan: Demography, Evolution, Medicine, and Bioengineering held at the Arnold and Mabel Beckman Center in Irvine, California, November 14-16, 2007. The discussions in these groups were summarized by the authors and reviewed by the members of each task group. Any opinions, findings, conclusions, or recommenda- tions expressed in this publication are those of the task groups and do not necessarily reflect the view of the organizations or agencies that provided support for this project. For more information on the National Academies Keck Futures Initiative, visit www. keckfutures.org. Funding for the activity that led to this publication was provided by the W.M. Keck Foundation. Based in Los Angeles, the W.M. Keck Foundation was established in 1954 by the late W.M. Keck, founder of the Superior Oil Company. The Foundation’s grant making is focused primarily on pioneering efforts in the areas of medical research, sci- ence, and engineering. The Foundation also maintains a Southern California Grant Program that provides support in the areas of civic and community services with a special emphasis on children. For more information, visit www.wmkeck.org. International Standard Book Number-13: 978-0-309-11559-9 International Standard Book Number-10: 0-309-11559-0 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu. Copyright 2008 by the National Academy of Sciences. All rights reserved. Printed in the United States of America

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The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a man- date that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Wm. A. Wulf is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the Na- tional Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council. www.national-academies.org

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THE NATIONAL ACADEMIES KECK FUTURES INITIATIVE HEALTHSPAN STEERING COMMITTEE JOHN ROWE, M.D. (Chair) (IOM), Professor of Health Policy and Management, Mailman School of Public Health, Columbia University STEVEN AUSTAD, Professor, Department of Cellular and Structural Biology, The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio VERN L. BENGTSON, AARP University Chair in Gerontology and Professor of Gerontology and Sociology, Leonard Davis School of Gerontology, University of Southern California ELIZABETH BLACKBURN (NAS/IOM), Morris Herzstein Professor of Biology and Physiology, Department of Biochemistry and Biophysics, University of California, San Francisco. JUDITH CAMPISI, Senior Scientist, Life Sciences Division, Lawrence Berkeley National Laboratory, Professor, Buck Institute for Age Research LAURA L. CARSTENSEN, Professor and Vice Chair and Director of the Stanford Center on Longevity, Stanford University RORY A. COOPER, Distinguished Professor, FISA/PVA Chair, Rehabilitation Science and Technology, University of Pittsburgh CALEB E. FINCH, ARCO-William F. Kieschnick Professor in the Neurobiology of Aging, and Co-Director, Alzheimer Disease Research Center, University of Southern California RICHARD J. HODES (IOM), Director, National Institute on Aging, National Institutes of Health RONALD LEE (NAS), Professor of Demography and Jordan Family Professor of Economics, Director, Center for the Economics and Demography of Aging, Department of Demography, University of California, Berkeley GEORGE M. MARTIN, M.D. (IOM), Professor of Pathology Emeritus, Director Emeritus Alzheimer’s Disease Research Center, University of Washington v

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ROBERT M. NEREM (NAE/IOM), Parker H. Petit Distinguished Chair for Engineering in Medicine, Institute Professor and Director of the Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology JAMES RIMMER, Professor and Director, National Center on Physical Activity and Disability, Rehabilitation Engineering Research Center on Recreational Technologies and Exercise Physiology for Persons with Disabilities, Department of Disability and Human Development, University of Illinois at Chicago MICHAEL ROSE, Professor, Department of Ecology and Evolutionary Biology, University of California, Irvine KHALED J. SALEH, M.D., Associate Professor Orthopedic Surgery and Health Evaluative Sciences Division, Division Head and Fellowship Director, Adult Reconstruction, University of Virginia SAVIO L-Y WOO (NAE/IOM), Ph.D, D.Sc, Whiteford Professor and Director, Musculoskeletal Research Center, Department of Bioengineering, University of Pittsburgh Staff KENNETH R. FULTON, Executive Director KIMBERLY SUDA-BLAKE, Program Director MEGAN ATKINSON, Senior Program Specialist ANNE HEBERGER, Research Associate RACHEL LESINSKI, Senior Program Specialist vi

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The National Academies Keck Futures Initiative The National Academies Keck Futures Initiative was launched in 2003 to stimulate new modes of scientific inquiry and break down the conceptual and institutional barriers to interdisciplinary research. The National Acad- emies and the W.M. Keck Foundation believe that considerable scientific progress will be achieved by providing a counterbalance to the tendency to isolate research within academic fields. The Futures Initiative is designed to enable scientists from different disciplines to focus on new questions, upon which they can base entirely new research, and to encourage and reward outstanding communication between scientists as well as between the sci- entific enterprise and the public. The Futures Initiative includes the following components: Futures Conferences bring together some of the nation’s best and brightest researchers from academic, industrial, and government labora- tories to explore and discover interdisciplinary connections in important areas of cutting-edge research. Each year some 100 outstanding research- ers are invited to discuss ideas related to a single cross-disciplinary theme. Participants gain not only a wider perspective but also, in many instances, new insights and techniques that might be applied in their own work. Additional pre- or postconference meetings build on each theme to foster further communication of ideas. Selection of each year’s theme is based on assessments of where the intersection of science, engineering, and medical research has the greatest vii

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viii THE naTIonal acaDEMIES kEck FUTURES INITIATIVE potential to spark discovery. The first conference, in 2003, explored Sig- nals, Decisions, and Meaning in Biology, chemistry, Physics, and Engineering. The 2004 conference focused on Designing nanostructures at the Interface between Biomedical and Physical Systems. The theme of the 2005 conference was The Genomic Revolution: Implications for Treatment and control of Infec- tious Disease. In 2006 the conference focused on Smart Prosthetics: Exploring assistive Devices for the Body and Mind. In 2007 the conference explored The Future of Human Healthspan: Demography, Evolution, Medicine, and Bioengineering, and in 2008 the conference will focus on complexity. Futures Grants provide seed funding to Futures Conference partici- pants, on a competitive basis, to enable them to pursue important new ideas and connections stimulated by the conferences. These grants fill a critical missing link between bold new ideas and major federal funding programs, which do not currently offer seed grants in new areas that are considered risky or exotic. These grants enable researchers to start developing a line of inquiry by supporting the recruitment of students and postdoctoral fellows, the purchase of equipment, and the acquisition of preliminary data, which in turn can position the researchers to compete for larger awards from other public and private sources. National Academies Communication Awards are designed to recog- nize, promote, and encourage effective communication of science, engineer- ing, medicine, and interdisciplinary work within and beyond the scientific community. Each year the Futures Initiative awards $20,000 prizes to those who have advanced the public’s understanding and appreciation of science, engineering, and/or medicine. Beginning in 2008, the awards will be given in four categories: books, newspaper/magazine, online, and TV/radio/film. The winners are honored during the Futures Conference. NAKFI cultivates science writers of the future by inviting graduate students from six science writing programs across the country to attend the conference and develop task group discussion summaries and a conference overview for publication in this book following the conference. Students are selected by the department director or designee, and prepare for the confer- ence by reviewing the webcast tutorials and suggested reading, and selecting a task group in which they would like to participate. Students then work with the task group to which they’re assigned to finish the report following the conferences.

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ix THE naTIonal acaDEMIES kEck FUTURES INITIATIVE FACILITATING INTERDISCIPLINARy RESEARCH STuDy During the first 18 months of the Keck Futures Initiative, the Acad- emies undertook a study on facilitating interdisciplinary research. The study examined the current scope of interdisciplinary efforts and provided recommendations as to how such research could be facilitated by fund- ing organizations and academic institutions. Facilitating Interdisciplinary Research (2005) is available from the National Academies Press (www.nap. edu) in print and free PDF versions. AbOuT THE NATIONAL ACADEMIES The National Academies comprise the National Academy of Sciences, the National Academy of Engineering, the Institute of Medicine, and the National Research Council, which perform an unparalleled public service by bringing together experts in all areas of science and technology, who serve as volunteers to address critical national issues and offer unbiased advice to the federal government and the public. For more information, visit www. national-academies.org. AbOuT THE W.M. KECK FOuNDATION Based in Los Angeles, the W.M. Keck Foundation was established in 1954 by the late W.M. Keck, founder of the Superior Oil Company. The Foundation’s grant making is focused primarily on pioneering efforts in the areas of medical research, science, and engineering. The Foundation also maintains a Southern California Grant Program that provides support in the areas of civic and community services with a special emphasis on children. For more information, visit www.wmkeck.org. The National Academies Keck Futures Initiative 100 Academy Irvine, CA 92617 949-721-2270 (Phone) 949-721-2216 (Fax) www.keckfutures.org

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Preface At the National Academies Keck Futures Initiative ConferenceThe Future of Human Healthspan: Demography, Evolution, Medicine, and Bioengi- neering, participants were divided into 12 interdisciplinary working groups. The groups spent eight hours over two days exploring diverse challenges at the interface between science, engineering, and medicine. The composition of the groups was intentionally diverse, to encourage the generation of new approaches by combining a range of different types of contributions. The groups included researchers from science, engineering, and medicine, as well as representatives from private and public funding agencies, universi- ties, businesses, journals, and the science media. Researchers represented a wide range of experience—from postdoc to those well established in their careers—from a variety of disciplines that included science and engineering, physical medicine and rehabilitation, biology, materials science, biomedical engineering, electrical engineering, chemistry, neuroscience, pharmacology, anatomy, genetics, and physics. The groups had to address the challenge of communicating and work- ing together from a diversity of expertise and perspectives as they attempted to solve a complicated interdisciplinary problem in a relatively short time. Each group decided on its own structure and approach to tackling the problem. Some groups decided to refine or redefine their problems based on their experience. Each group presented two brief reports to the whole conference: (1) an interim report on Thursday to debrief on how things were going, along xi

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xii PREFacE with any special requests (such as an expert in inflammation) and (2) a final briefing on Friday, when each group: • provided a concise statement of the problem; • outlined a structure for its solution; • identified the most important gaps in science and technology and recommended research areas needed to attack the problem; and • indicated the benefits to society if the problem could be solved. Each task group included a graduate student in a university science writing program. Based on the group interaction and the final briefings, the students wrote the following summaries, which were reviewed by the group members. These summaries describe the problem and outline the approach taken, including what research needs to be done to understand the funda- mental science behind the challenge, the proposed plan for engineering the application, the reasoning that went into it, and the benefits to society of the problem solution. Eight webcast tutorials were held in September to help bridge the gaps in terminology used by the various disciplines. Participants had the oppor- tunity to ask questions of the webcast speakers during panel sessions, prior to dividing into their task groups.

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Contents Conference Summary 1 TASK GROuP SuMMARIES Enhancing the Functional Status of the Future Elderly 7 Design New Research Paradigms to Assess Healthspan, Its Enhancement, and Prolongation in Experimental Research Animals 17 Task Group Summary A, 19 Task Group Summary B, 24 Effects of Exercise on Human Healthspan 29 The Relationship Between Demographic Mortality Rates, Aging, and Functional Human Healthspan 41 Changes in Social Contexts to Enhance Functional Status of the Elderly 49 Develop Technological Interventions to Overcome Barriers to Independence and Community Participation 57 Task Group Summary A, 62 Task Group Summary B, 65 xiii

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xiv conTEnTS Cellular and Molecular Mechanisms of Biological Aging: The Roles of Nature, Nurture, and Chance in the Maintenance of Human Healthspan 73 Task Group Summary A, 78 Task Group Summary B, 84 Task Group Summary C, 88 Inflammation’s Effects on Aging 93 APPENDIXES Preconference Webcast Tutorials 103 Agenda 107 Participants 113 To view the preconference webcast tutorials or conference presenta- tions, please visit our website at www.keckfutures.org.