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Diverse Biology of the Gut Featured in Science
Gastroenterology News Obesity Threatens U.S. Life Expectancy
O
ver the next few decades, life expectancy for the average American could decline by as much as 5 years unless aggressive efforts are made to slow rising rates of obesity, according to a report in The New England Journal of Medicine. The report warns that the U.S. could be facing its first sustained drop in life expectancy in the modern era, but this decline is not inevitable if Americans—particularly young people—trim their waistlines or if other improvements outweigh the impact of obesity. The report appears little more than a year after the Department of Health and Human Services unveiled a new national education campaign and research strategy to combat obesity and excessive weight. The new analysis, by Dr. S. Jay Olshansky, professor of epidemiology at the University of Illinois at Chicago, Dr. Leonard Hayflick, professor of anatomy at the University of California, San Francisco, Dr. Robert N. Butler of the International Longevity Center in New York, and others suggests that the methods used to establish life expectancy projections, which have long been based on historic trends, need to be reassessed. This re-evaluation is particularly important, they say, as obesity rates surge in today’s children and young adults. “Forecasting life expectancy by extrapolating from the past is like forecasting the
Diverse Biology of the Gut Featured in Science
B
eginning with a cover photo of a colored barium x-ray image of the colon in the early stages of Crohn’s disease, the March 25 issue of the journal Science contains an editorial and special section that features the diverse biology of the human gut. The
GASTROENTEROLOGY 2005;128:1156 –1157
weather on the basis of its history,” Olshansky and his colleagues write. “Looking out the window, we see a threatening storm— obesity—that will, if unchecked, have a negative effect on life expectancy.” Unlike historic life expectancy forecasts, which rely on past mortality trends, the study group based their projection on an analysis of body mass indexes and other factors that could potentially affect the health and well-being of the current generation of children and young adults, some of whom began having weight problems very early in life. The authors say that unless steps are taken to curb excessive weight gain, younger Americans will likely face a greater risk of mortality throughout life than previous generations. “This work paints a disturbing portrait of the potential effect that lifestyles of baby boomers and the next generation could have on life expectancy,” says Dr. Howard M. Suzman, associate director of the National Institute on Aging, which provided support for the study. Suzman notes that obesity may already have had an effect. The sharp increase of obesity among people now in their 60s, he suggests, may be one explanation why the gains in U.S. life expectancy at older ages have been less than those of other developed countries in recent years. “But it is critical to note that the reduced life expectancy forecast by the study is not inevitable, and there is room for optimism,” he says. “Gov-
ernment and private sector efforts are mobilizing against obesity, and increased education, improved medical treatments, and reduced smoking can tip the balance in favor of reduced mortality and continued improvements in life expectancy.” This view is echoed in an editorial that accompanies the NEJM report. “The fact that the U.S. population has already shown the ability to shift to healthier lifestyles is encouraging,” writes Dr. Samuel H. Preston, Fredrick J. Warren professor of demography at the University of Pennsylvania. He points out that 42% of U.S. adults were smokers in 1965, as compared with 23% in 2001, and that the percentage of Americans 20 to 74 years of age with high levels of serum cholesterol fell from 33% in 1961 to 18% in 1999 and 2000. “Primarily because of behavioral changes, the incidence of AIDS has fallen by nearly 50% since 1992,” he adds. “The fact that most health-related behaviors have improved while obesity has worsened may be an indication of just how daunting the prospect of reducing levels of obesity may be. The rising prevalence and severity of obesity are already reducing life expectancy among the U.S. population. A failure to address the problem could impede the improvements in longevity that are otherwise in store.” For more details, see The New England Journal of Medicine, March 17, 2005, vol 352, 1138 –1145; 1135–1137.
section explores the abundant yet largely unknown microorgansisms it harbors, its normal functions of digestion and delivery of nutrients, and the diseases to which it is prone. In his editorial, “Cancers of the Gut and Western Ills,” Dr. Ian T. Johnson, head of the Gastrointestinal Biology and Health Programme at
the Biological Sciences Research Council in the UK, states that despite the huge progress made in understanding the molecular basis of many cancers in recent years, “most of the new knowledge has been deployed in the search for new therapies rather than to understand the role of nutrition in their causation.” John-
Gastroenterology News continued
son says the mechanisms linking diet to cancer “can be understood and exploited” for both prevention and treatment, and he points to several “scientific and strategic reasons to focus such research on carcinomas of the alimentary tract.” These include evidence in support of “overnutrition” as a factor in an increased risk of bowel cancer within population of the developed world, “where overconsumption of energy, low levels of physical activity, high body mass index, and abdominal obesity are strong independent risk factors for colorectal carcinoma.” He also notes evidence for a link between obesity and esophageal cancer, once rare “but now advancing rapidly throughout North America and Western Europe.” Johnson sees “little evidence” to support the view that alimentary cancers are tied to the adverse effects in the diet of food-borne carcinogens, despite the presence of mutagens in low concentrations in foods and feces. “It seems more plausible that the Western gut become vulnerable to neoplasia because of adverse
metabolic factors, such as pro-inflammatory enzymes in precancerous tissues, and because of low intakes of anti-carcinogens from plant foods.” He asserts that the role of weight, lack of exercise, and inadequate consumption of plant foods in the etiology of gut cancers “needs to be more widely acknowledged and publicized.” This special section in the journal also contains articles on the pathogenic potential of microbial communities that thrive on and around teeth, gums, and the tongue; gut development and evolution; the gut and energy balance; host-bacterial “mutualism” in the gut; and immunity, inflammation, and allergy in the gut. Also included in this issue of Science is a report from Johns Hopkins University School of Medicine, the National Institute on Aging, and Keio University School of Medicine in Tokyo, Japan, that suggests a cellular mechansim by which epigenetic alterations in normal cells may affect cancer risk. In the study, loss of imprinting of the insulin-like growth factor II gene (Igf2) is tied to alter-
ations in intestinal maturation and tumorigenesis in mice. According to the authors, such an epigenetic change may serve as a possible marker for cancer screening. They note that a “modest increase in Igf2 expression” resulting from this change is present in the normal colonic mucosa of roughly 30% of patients with colorectal cancer. The study involved a loss of imprinting (LOI) mouse model in which LOI mice developed twice as many intestinal tumors as did control littermates. These mice also showed a shift toward a less differentiated normal intestinal epithelium, as shown by an increase in crypt length and increased staining with progenitor cell markers. “A similar shift in differentiation was seen in the normal colonic mucosa of humans with LOI. Thus, altered maturation of non-neoplastic tissue may be one mechanism by which epigenetic changes affect cancer risk,” the authors state. For more detail, see Science vol. 307, 25 March 2005. Stories by Les Lang
1157
O
ver the next few decades, life expectancy for the average American could decline by as much as 5 years unless aggressive efforts are made to slow rising rates of obesity, according to a report in The New England Journal of Medicine. The report warns that the U.S. could be facing its first sustained drop in life expectancy in the modern era, but this decline is not inevitable if Americans—particularly young people—trim their waistlines or if other improvements outweigh the impact of obesity. The report appears little more than a year after the Department of Health and Human Services unveiled a new national education campaign and research strategy to combat obesity and excessive weight. The new analysis, by Dr. S. Jay Olshansky, professor of epidemiology at the University of Illinois at Chicago, Dr. Leonard Hayflick, professor of anatomy at the University of California, San Francisco, Dr. Robert N. Butler of the International Longevity Center in New York, and others suggests that the methods used to establish life expectancy projections, which have long been based on historic trends, need to be reassessed. This re-evaluation is particularly important, they say, as obesity rates surge in today’s children and young adults. “Forecasting life expectancy by extrapolating from the past is like forecasting the
Diverse Biology of the Gut Featured in Science
B
eginning with a cover photo of a colored barium x-ray image of the colon in the early stages of Crohn’s disease, the March 25 issue of the journal Science contains an editorial and special section that features the diverse biology of the human gut. The
GASTROENTEROLOGY 2005;128:1156 –1157
weather on the basis of its history,” Olshansky and his colleagues write. “Looking out the window, we see a threatening storm— obesity—that will, if unchecked, have a negative effect on life expectancy.” Unlike historic life expectancy forecasts, which rely on past mortality trends, the study group based their projection on an analysis of body mass indexes and other factors that could potentially affect the health and well-being of the current generation of children and young adults, some of whom began having weight problems very early in life. The authors say that unless steps are taken to curb excessive weight gain, younger Americans will likely face a greater risk of mortality throughout life than previous generations. “This work paints a disturbing portrait of the potential effect that lifestyles of baby boomers and the next generation could have on life expectancy,” says Dr. Howard M. Suzman, associate director of the National Institute on Aging, which provided support for the study. Suzman notes that obesity may already have had an effect. The sharp increase of obesity among people now in their 60s, he suggests, may be one explanation why the gains in U.S. life expectancy at older ages have been less than those of other developed countries in recent years. “But it is critical to note that the reduced life expectancy forecast by the study is not inevitable, and there is room for optimism,” he says. “Gov-
ernment and private sector efforts are mobilizing against obesity, and increased education, improved medical treatments, and reduced smoking can tip the balance in favor of reduced mortality and continued improvements in life expectancy.” This view is echoed in an editorial that accompanies the NEJM report. “The fact that the U.S. population has already shown the ability to shift to healthier lifestyles is encouraging,” writes Dr. Samuel H. Preston, Fredrick J. Warren professor of demography at the University of Pennsylvania. He points out that 42% of U.S. adults were smokers in 1965, as compared with 23% in 2001, and that the percentage of Americans 20 to 74 years of age with high levels of serum cholesterol fell from 33% in 1961 to 18% in 1999 and 2000. “Primarily because of behavioral changes, the incidence of AIDS has fallen by nearly 50% since 1992,” he adds. “The fact that most health-related behaviors have improved while obesity has worsened may be an indication of just how daunting the prospect of reducing levels of obesity may be. The rising prevalence and severity of obesity are already reducing life expectancy among the U.S. population. A failure to address the problem could impede the improvements in longevity that are otherwise in store.” For more details, see The New England Journal of Medicine, March 17, 2005, vol 352, 1138 –1145; 1135–1137.
section explores the abundant yet largely unknown microorgansisms it harbors, its normal functions of digestion and delivery of nutrients, and the diseases to which it is prone. In his editorial, “Cancers of the Gut and Western Ills,” Dr. Ian T. Johnson, head of the Gastrointestinal Biology and Health Programme at
the Biological Sciences Research Council in the UK, states that despite the huge progress made in understanding the molecular basis of many cancers in recent years, “most of the new knowledge has been deployed in the search for new therapies rather than to understand the role of nutrition in their causation.” John-
Gastroenterology News continued
son says the mechanisms linking diet to cancer “can be understood and exploited” for both prevention and treatment, and he points to several “scientific and strategic reasons to focus such research on carcinomas of the alimentary tract.” These include evidence in support of “overnutrition” as a factor in an increased risk of bowel cancer within population of the developed world, “where overconsumption of energy, low levels of physical activity, high body mass index, and abdominal obesity are strong independent risk factors for colorectal carcinoma.” He also notes evidence for a link between obesity and esophageal cancer, once rare “but now advancing rapidly throughout North America and Western Europe.” Johnson sees “little evidence” to support the view that alimentary cancers are tied to the adverse effects in the diet of food-borne carcinogens, despite the presence of mutagens in low concentrations in foods and feces. “It seems more plausible that the Western gut become vulnerable to neoplasia because of adverse
metabolic factors, such as pro-inflammatory enzymes in precancerous tissues, and because of low intakes of anti-carcinogens from plant foods.” He asserts that the role of weight, lack of exercise, and inadequate consumption of plant foods in the etiology of gut cancers “needs to be more widely acknowledged and publicized.” This special section in the journal also contains articles on the pathogenic potential of microbial communities that thrive on and around teeth, gums, and the tongue; gut development and evolution; the gut and energy balance; host-bacterial “mutualism” in the gut; and immunity, inflammation, and allergy in the gut. Also included in this issue of Science is a report from Johns Hopkins University School of Medicine, the National Institute on Aging, and Keio University School of Medicine in Tokyo, Japan, that suggests a cellular mechansim by which epigenetic alterations in normal cells may affect cancer risk. In the study, loss of imprinting of the insulin-like growth factor II gene (Igf2) is tied to alter-
ations in intestinal maturation and tumorigenesis in mice. According to the authors, such an epigenetic change may serve as a possible marker for cancer screening. They note that a “modest increase in Igf2 expression” resulting from this change is present in the normal colonic mucosa of roughly 30% of patients with colorectal cancer. The study involved a loss of imprinting (LOI) mouse model in which LOI mice developed twice as many intestinal tumors as did control littermates. These mice also showed a shift toward a less differentiated normal intestinal epithelium, as shown by an increase in crypt length and increased staining with progenitor cell markers. “A similar shift in differentiation was seen in the normal colonic mucosa of humans with LOI. Thus, altered maturation of non-neoplastic tissue may be one mechanism by which epigenetic changes affect cancer risk,” the authors state. For more detail, see Science vol. 307, 25 March 2005. Stories by Les Lang
1157