Should scientists subject humans to research studies on CR to see whether it produces the same results in humans as in lab animals? What effect will CR have on psychosocial health and quality of life? Should CR replace other human weight-control strategies? Is CR even possible given the fact that humans have unrestricted access to food?
To answer these and other questions, the National Institute on Aging in collaboration with the National Institute of Diabetes, Digestive, and Kidney Diseases convened the Caloric Restriction Clinical Implications (CRCI) Advisory Group to consider opportunities of such research. The group, which included gerontologists, nutritionists, pharmacologists, physicians, and psychologists, published their findings and recommendations in a special issue of the Journals of Gerontology Series A: Biological Sciences and Medical Sciences (Special Issue I, March 2001, http://www.geron.org/journals/spcontents.html).
Caloric restriction is accomplished by restricting caloric intake far below what an animal would consume on its own. In animal studies, CR was found to extend life expectancy by 30 to 40 percent if initiated in early adulthood.
A panel of experts led by I-Min Lee of Harvard Medical School looked at whether there are physiological effects that occur with CR in humans that could plausibly explain the observed longevity of lab animals associated with CR. They also wrestled with the appropriate CR model in humans. Is it being thin over most of adult life or not gaining weight over time or expending more calories than eaten or eating fewer calories? And more importantly is CR feasible?
Caloric restriction retards diseases and aging among lab rodents, and is now being tested in nonhuman primates with the goal to eventually identify and test agents that may mimic critical actions of CR. The second panel led by Richard Weindruch of the Department Medicine at the University of Wisconsin focused on outcomes of two such agents, oxidative stress and improved glucoregulation.
One aspect of the lab animal paradigm of CR is clearly not applicable to human intervention studies: its involuntary nature. Almost all humans have unlimited access to food, so that some degree of volition must be involved. Panel 3 led by Charles V. Mobbs of the Departments of Neurobiology and Geriatrics at New York's Mount Sinai School of Medicine, assessed the effects of long-term involuntary food restriction.
The distinction between "pure" caloric intake-reducing interventions and alternative weight-loss interventions relates to an issue of practical and mechanistic importance: whether changes in exercise and body composition produce similar changes as those found in dietary restriction. Panel 4 led by Eric Poehlman of the Department of Medicine at the University of Vermont addressed this issue.
Panel 5 led by David B. Allison of the Obesity Research Center at St.Luke's-Roosevelt Hospital in New York focused on genetic factors that might mediate or moderate the effects of CR on longevity. Is there evidence of genetic factors causing variability of the effects of CR on life span and/or age related pathologies? The panel found at least three reasons why it should be valuable to find genes that influence the longevity-promoting effect of CR in humans.
Susan B. Roberts of USDA Human Nutrition Research Center on Aging at Tufts University and her team in Panel 6 recommend medium-term intervention studies in non-obese persons to test benefits of weight-loss interventions against obesity. The panel concluded that the CR benefit in human populations has to be established, so studies in human population are needed to find out whether CR can provide the benefits that have been found in lab animals.
The reports by the Advisory Group presented in the Journals of Gerontology: Biological Sciences and Medical Sciences look at the clinical and basic research opportunities for CR research among humans. The recommendations by the Advisory Group can provide the road map for developing such research.
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences (http://www.gerontologyjournals.org)are refereed publications of The Gerontological Society of America, the national organization of professionals in the field of aging.
Journal
The Journals of Gerontology Series A