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Effects of Exercise on Human Healthspan TASK GROuP DESCRIPTION background It is well recognized that motion and exercise have substantial benefits in increasing human health, cognitive and physical function, quality of life, and longevity. However, the dose-response effects of exercise on improving certain systems and increasing the lifespan and healthspan have not been well elucidated. Given the aging populations, there is an increasing interest in lifestyle factors and interventions that will enhance the cognitive and physical vitality of older adults and reduce the risk for age-related neurologi- cal and functional disorders, such as Alzheimer’s disease and hip fractures. But the knowledge concerning the applicability and the effect of moderate- to high-intensity exercise programs is very limited for older people with or without apparent cognitive and physical impairments. Initial Challenges to Consider • What are the social, psychological, cognitive, physical, and physi- ological benefits of exercise in increasing the human healthspan? It is im- portant to establish an age-related dose response curve. What should be a desirable goal for a healthy 70-, 80-, or 90-year-old? • What are the benefits of exercise in the prevention of injury resulting from lack of musculoskeletal coordination and cognitive deficits? 

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0 THE FuTuRE oF HuMan HEalTHSPan • How to develop sensitive outcome measures of exercise over inactiv- ity at the molecular, cellular, tissue, and functional levels to show positive effects of exercise? • How to develop experimental models for use by the human population? • Given that physical activity is an inexpensive treatment that could have substantial preventive and restorative benefits for cognitive and brain function, how can such interventions be studied and how can they be implemented on a population-based scale? • How will technology (e.g., novel equipment, improved environ- ment) facilitate and motivate people to exercise on a regular basis? Specif- ics should include how technological innovation will make exercise more attractive and compelling for cardiovascular and musculoskeletal systems improvement (e.g., aerobic and resistance exercise). • How can we change community design in rural, suburban, and urban settings to facilitate and encourage as well as promote exercise in younger and older populations? What are the recommended strategies for such enhancement? Initial References Bourdel-Marchasson, I., M. Biran, P. Dehail, T. Traissac, F. Muller, J. Jenn, G. Raffard, J. M. Franconi, and E. Thiaudiere. 2007. Muscle phosphocreatine post-exercise recovery rate is related to functional evaluation in hospitalized and community-living older people. Journal of Nutrition and Health and Aging 11(3):215-221. Buckwalter, J. A., V. M. Goldberg, and S. L-Y Woo (eds.). 1993. Musculoskeletal tissue aging: Impact on mobility. Chicago, Ill: American Academy of Orthopaedic Surgeons. Hardy, S. E., and T. M. Gill. 2005. Factors associated with recovery of independence among newly disabled older persons. Archives of Internal Medicine 165(1):106-112. Judge, J. O., C. Lindsey, M. Underwood, and D. Winsemius. 1993. Balance improvements in older women: Effects of exercise training. Physical Therapy 73(4):254-262. Kramer, A. F., S. J. Colcombe, E. McAuley, P. E. Scalf, and K. I. Erickson. 2005. Fitness, aging and neurocognitive function. Neurobiology of Aging 26(suppl. 1):124-127. Littbrand, H., E. Rosendahl, N. Lindelöf, L. Lundin-Olsson, Y. Gustafson, and L. Nyberg. 2006. A high intensity functional weight-bearing exercise program for older people dependent in activities of daily living and living in residential care facilities: Evaluation of the applicability with focus on cognitive function. Physical Therapy 86(4):489- 498. Mangione, K. K., and K. M. Palombaro. 2005. Exercise prescription for a patient 3 months after hip fracture. Physical Therapy 85(7):676-687.

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 EFFEcTS oF ExERcISE on HuMan HEalTHSPan Marottoli, R. A., H. Allore, K. L. B. Araujo, P. H. Van Ness, L. P. Iannone, D. Acampora, P. Charpentier, and P. Peduzzi. 2007. A randomized trial of a physical conditioning program to enhance the driving performance of older persons. Journal of General Internal Medicine 22:590-597. Melov, S., M. A. Tarnopolsky, K. Beckman, K. Felkey, and A. Hubbard. 2007. Resistance exercise reverses aging in human skeletal muscle. PLoS ONE 2(5):e465 (www.plosone. org). Messier, S. P., R. F. Loeser, M. N. Mitchell, G. Valle, T. P. Morgan, W. J. Rejeski, and W. H. Etinger. 2000. Exercise and weight loss in obese older adults with knee osteoarthritis: A preliminary study. Journal of the American Geriatric Society 48(9):1062-1072. Wu, S. C., S. Y. Leu, and C. Y. Li. 1999. Incidence of and predictors for chronic disability in activities of daily living among older people in Taiwan. Journal of the American Geriatric Society 47(9):1082-1086. Task Group Members • Albert Banes, North Carolina State University • Bambi Brewer, University of Pittsburgh • Nadeen Chahine, Lawrence Livermore National Laboratory • Nandini Deshpande, University of Kansas Medical Center • Stephen Intille, Massachusetts Institute of Technology • Robert Jaeger, National Science Foundation • Richard Macko, University of Maryland School of Medicine • Charlotte A. Tate, University of Illinois at Chicago • Geoffrey Graybeal, University of Georgia TASK GROuP SuMMARy By Geoffrey M. Graybeal, Graduate Writing Student, Grady college of Journalism and Mass communication, university of Georgia IRVINE, CALIF.—An interdisciplinary group of scientists and researchers has written a prescription to improve the human healthspan: Exercise. “Exercise as medicine” was one of several key ideas discussed by this task group at the National Academies Keck Futures Initiative’s The Future of Human Healthspan conference. During November 14-16, 2007, at the Arnold and Mabel Beckman Center of the National Academies, this particular task group spent two days examining the topic of the effects of exercise on human healthspan. The group concluded that exercise could follow the pharmaceutical

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 THE FuTuRE oF HuMan HEalTHSPan model in which doctors prescribe doses, such as amount and frequencies, in order to promote better health and combat diseases. “Exercise is a pill. There’s dose intensity to it,” said Dr. Richard Macko, an associate researcher for the Baltimore Geriatric Research, Education, and Clinical Center and associate professor in the departments of neurology and gerontology at the University of Maryland and the Baltimore Veterans Af- fairs Medical Center. Macko served as chairman of the task group. The practice gap between the medical community and the health community is huge, Macko told group members, who wondered whether a physician-recommended prescription of exercise would affect exercise re- sults. For stroke victims there is evidence that a physician’s recommendation affects patient efficacy, Macko told his colleagues in the group. The exercise prescription could positively alter the health care of patients with chronic diseases, such as diabetes and hypertension. Group members discussed the importance of linking the medical requirement of exercise as a form of medical care, and also to provide continuity between the medical community, private sector, and government agencies and com- munity advocacy organizations. Dr. Charlotte (“Toby”) Tate, dean of the College of Applied Health Science at the University of Illinois at Chicago, noted that the American College of Sports Medicine and the American Medical Association recently started an Exercise is Medicine™ initiative. One problem with that new program has been that primary care doctors typically haven’t had exercise or nutrition training in medical school, Tate said. This raises the question of how to provide the desired continuity between the health and medical sectors, according to Tate. Group members wanted to explore the possibility of expanding elec- tronic medical records so that they could be accessed from any location, and also having exercise efforts become a performance measure that could be tracked. “If these recommendations don’t have teeth they’re going to be wallflowers,” remarked one member. The medical community should make exercise as medicine more pervasive than giving pills, said John Doyle, of the California Institute of Technology, a floater, who spent a great deal of time with this task group. The biggest problem, or inadequacy, however, he noted is what engineers call system integration. The drug industry spends billions of dollars on advertising to get the drugs into people’s hands. A similar, across-the-board “full-court press” is needed for prescribing exercise, Doyle said. The group generally agreed that exercise should be treated as a medi-

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 EFFEcTS oF ExERcISE on HuMan HEalTHSPan FIGURE 1 The grand integration challenge. cine, prescribed and tracked and efforts to promote exercise moved into the community and corporate sector. The group largely agreed that technology use could encourage exercise activities and that business could play a role in supporting research initiatives. Group members would like for the societal model to be linked with the medical model and a socioeconomic model also explored (see Figure 1 for an illustration of this grand integration challenge). “Is exercise important regardless of any of the other issues?” was a question that was posed. The evidence is yes, the group said. In addition to prescribing the exercise-as-medicine approach, members of the task group would also like to see more people join the dance (dance) revolution, work toward a “SustainableYou,” get a “SecondLife with exercise in it,” go green to reduce their carbon footprint, and see more displays of “PDA.” These were among the more creative solutions bandied about by members of this task group. No, the researchers don’t want to see public displays of affection. Nor do they believe personal digital assistants like Blackberrys or Treos are the answer either. The PDA the group envisions are “Purpose Driven Activi- ties,” a term suggested by Dr. Al Banes, a biomedical engineering researcher with a joint appointment to the University of North Carolina and North Carolina State University. The activities could include encouraging people to walk to school, work, and house of worship and organizations could part- ner with existing community efforts, such as the Rails-to-Trails organization that converts abandoned railroad trestles into walking paths.

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 THE FuTuRE oF HuMan HEalTHSPan One idea tossed around was a community program that would pair senior citizens with young children, where both would walk to school. One member noted that walking to school, rather than busing would be a great idea and that with gasoline prices continually escalating, this could be a forced reality. The “SustainableYou” idea was proposed by Doyle as a campaign to connect physical activity to the greater issue of sustainability and global warming as a means of reducing an individual’s carbon footprint. The group discussed ways to encourage movement among kids and adults, ways to integrate movement into their everyday lives. The Nin- tendo Wii home video gaming system, in which users physically swing the controller, and Dance Dance Revolution arcade game, in which users hop from square to square, were cited as appealing means of technology that encourage physical activity but at the same time are popular and widely used. The group considered what other sort of technologies could be used in a similar fashion to tap into the public’s competitive nature and love of games. Virtual reality programs that would allow a variety of physical chal- lenges in a competitive environment were considered. “We need a Star Trek holodeck,” Banes said, referencing the simulator on the futuristic spaceship in the popular science fiction television series. “We need a SecondLife with exercise in it,” Doyle later added, referring to a popular online virtual community. Business can be a powerful influencer of change, it was also noted. Some insurance companies use pedometers to track movement and if cus- tomers are participating they receive lower rates. The question of whether insurance companies and business provide enough incentives to get people to comply with good health was raised. Group members also would like to call for the creation of a new exer- cise-monitoring device that will give positive feedback to encourage people to continue exercising. Such a device could include features such as a cell phone/wrist watch energy expenditure monitor, a SustainableYou carbon count monitor, and a dietary adviser that could help with meal suggestions, estimation of caloric intake, etc. Problems Before coming up with these possible solutions, the group grappled with meta-issues related to its task. The earlier discussion focused on the distinction between exercise and physical activity, the issue of whether the

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 EFFEcTS oF ExERcISE on HuMan HEalTHSPan group should focus its efforts on exercise activities for disabled populations, the general populace, or both; how to treat technology initiatives; and an operational definition of what exactly “compliance” means. Throughout the discussion the group realized that much of what is needed is outside of the realm of the hard sciences. A large part of the dis- cussion centered on social science issues, such as how to motivate people to act, how to disseminate information and campaigns to the public, and the importance of moving efforts out of the lab and into the community. Group consensus was that moving beyond RCTs (randomized controlled trials) requires partnership and buy-in with community groups, businesses, and perhaps in some instances, with insurance providers. Trials for every form of exercise are not practical, a group member noted. Finding ways to motivate the public to exercise was a continual focus of the conversations. Stephen Intille, technology director of the House_n Consortium in the MIT Department of Architecture suggested that technology might be used in innovative ways to ease people into exercise, diminishing the mental and physiological barriers to getting started. Many sedentary activities are instantly fun and engaging, such as watching a television show, snacking, or reading a book, while the payoff from exercise is typically far more delayed and subtle (as illustrated in Figures 2-6). FIGURE 2 Ease of access to food.

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6 THE FuTuRE oF HuMan HEalTHSPan FIGURE 3 Exercise. FIGURE 4 Perfect story (+ sedentarism).

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 EFFEcTS oF ExERcISE on HuMan HEalTHSPan FIGURE 5 Research challenge: Fill compliance void. FIGURE 6 Research challenge: Get compliance/offset pain.

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 THE FuTuRE oF HuMan HEalTHSPan The author (Graybeal) noted that health communication is a bour- geoning field that receives a fair amount of funding from government organizations like the Centers for Disease Control and Prevention. Health communication professionals design campaigns aimed at communicat- ing health initiatives and messages to the public. Graybeal suggested that researchers could partner with health communicators to disseminate their research by developing programs and messages to the public at large and specific community groups in particular. Some other problems the task group identified include: • Getting longitudinal, community-based studies funded; • There are not enough good measurements of the efficacy of exercise; • The secondary conditions that affect exercise among the disabled community, including pain, fatigue, depression, and social isolation; • A deficit in existing technology to effectively monitor various exer- cise functions; • Existing care of chronic diseases, which are a big expense in the health care system and a top cause of death; • A knowledge gap between scientists and the public, and desensitiza- tion of the public to recommendations due to inconclusive evidence that leads to recommendation changes; and • The existing government recommendations for daily activity are difficult for many Americans to interpret (What is “moderate intensity” or “brisk walking”?). Future Challenges The group agreed that further research is needed in the following areas: • Exploratory development of innovative technology for exercise; • Measurement of time-duration-intensity or dose-response; • Measurement of relationship between environment and physical activity; • Research on novel ways to use technology to create incentives, com- pliance, motivation; • Research on how to provide continuity in exercise prescription and

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 EFFEcTS oF ExERcISE on HuMan HEalTHSPan compliance between medical, private sector, and community advocacy organizations; and • Implementation and tracking of new guidelines from the Depart- ment of Health and Human Services. Some research questions that were developed: 1. Dosage of exercise: Investigate relationship between low levels of activity with health measures. 2. How short can the exercise dose be and remain effective? Optimize exercise dose in order to incorporate effectively into everyday activity. 3. Which outcomes do you pursue? Calories, lean or fat, body weight mass, absolute weight, weight maintenance, cardiovascular fitness, blood pressure, heart rate, flexibility, muscle strength, pain, feelings of wellness? 4. Use technology to motivate people to transition to higher levels or stages of change with respect to physical activity. 5. Enable some progress in metrics toward improving activity level. 6. Create technology that correlates health measures with customiz- able reward. 7. Education programs: teaching children how to exercise as adults (study of group activity vs. personal activity). 8. Sensors with feedback: clothing, wrist watch, breathing rate, pe- dometers, schedule with reminders, report to user and/or doctor. 9. Biosensors: muscle tonicity, biochemical or gene response with exercise, cellular response to exercise, blood flow, electrophysiological measure, heat/energy, calories burned, wattage, fat loss, improve insulin sensitivity. 10. How does exercise affect cellular/molecular measures, mechano- sensitivity, and stretch-activated channels? 11. Magic drug to motivate people to exercise? Can we identify mol- ecules that motivate people to comply with exercise programs? Improve insulin sensitivity, effect of Viagra on skeletal muscle performance. 12. Activity monitoring in real time: sensitive quantification of ac- tivity, prevention of decline, feedback to health care provider, therapists, researchers, and users, and 13. Endocrinology and neuroendocrinology of aging, exercise, and cognition: effect of growth factors, anabolic steroids, hormone supplementation.

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