Review of the International Research Conference on Food, Nutrition, and Cancer, 2004 (original) (raw)
Related papers
Calorie Restriction, Aging, and Cancer Prevention: Mechanisms of Action and Applicability to Humans*
Annual Review of Medicine, 2003
Key Words carcinogenesis, insulin-like growth factor-1, apoptosis, reactive oxygen species s Abstract Calorie restriction (CR) is the most effective and reproducible intervention for increasing lifespan in a variety of animal species, including mammals. CR is also the most potent, broadly acting cancer-prevention regimen in experimental carcinogenesis models. Translation of the knowledge gained from CR research to human chronic disease prevention and the promotion of healthy aging is critical, especially because obesity, which is an important risk factor for several chronic diseases, including many cancers, is alarmingly increasing in the Western world. This review synthesizes the key biological mechanisms underlying many of the beneficial effects of CR, with a particular focus on the insulin-like growth factor-1 pathway. We also describe some of the opportunities now available for investigations, including gene expression profiling studies, the development of pharmacological mimetics of CR, and the integration of CR regimens with targeted, mechanism-based interventions. These approaches will facilitate the translation of CR research into strategies for effective human chronic disease prevention.
Calorie restriction: what recent results suggest for the future of ageing research
European Journal of Clinical Investigation, 2010
Background-Calorie Restriction (CR) research has expanded rapidly over the past few decades and CR remains the most highly reproducible, environmental intervention to improve health and extend lifespan in animal studies. Although many model organisms have consistently demonstrated positive responses to CR, it remains to be shown whether CR will extend lifespan in humans. Additionally, the current environment of excess caloric consumption and high incidence of overweight/obesity illustrate the improbable nature of the long-term adoption of a CR lifestyle by a significant proportion of the human population. Thus, the search for substances that can reproduce the beneficial physiologic responses of CR without a requisite calorie intake reduction, termed CR mimetics (CRMs), has gained momentum. Material & Methods-Recent articles describing health and lifespan results of CR in nonhuman primates and short-term human studies are discussed. Additional consideration is given to the rapidly expanding search for CRMs. Results-The first results from a long-term, randomized, controlled CR study in nonhuman primates showing statistically significant benefits on longevity have now been reported. Additionally, positive results from short-term, randomized, controlled CR studies in humans are suggestive of potential health and longevity gains, while test of proposed CRMs (including rapamycin, resveratrol, 2-deoxyglucose and metformin) have shown both positive and mixed results in rodents. Conclusion-Whether current positive results will translate into longevity gains for humans remains an open question. However, the apparent health benefits that have been observed with CR suggest that regardless of longevity gains, the promotion of healthy aging and disease prevention may be attainable.
Scientific Reports, 2016
Both chronic calorie restriction (CCR) and intermittent calorie restriction (ICR) have shown anticancer effects. However, the direct evidence comparing ICR to CCR with respect to cancer prevention is controversial and inconclusive. PubMed and Web of Science were searched on November 25, 2015. The relative risk (RR) [95% confidence interval (CI)] was calculated for tumor incidence, and the standardised mean difference (95% CI) was computed for levels of serum insulin-like growth factor-1 (IGF-1), leptin, and adiponectin using a random-effects meta-analysis. Sixteen studies were identified, including 11 using genetically engineered mouse models (908 animals with 38-76 weeks of follow-up) and 5 using chemically induced rat models (379 animals with 7-18 weeks of follow-up). Compared to CCR, ICR decreased tumor incidence in genetically engineered models (RR = 0.57; 95% CI: 0.37, 0.88) but increased the risk in chemically induced models (RR = 1.53, 95% CI: 1.13, 2.06). It appears that ICR decreases IGF-1 and leptin and increases adiponectin in genetically engineered models. Thus, the evidence suggests that ICR exerts greater anticancer effect in genetically engineered mouse models but weaker cancer prevention benefit in chemically induced rat models as compared to CCR. Further studies are warranted to confirm our findings and elucidate the mechanisms responsible for these effects. Cancer is, to some extent, a preventable disease that is presumably caused by a combination of genetic, environmental, and behavioural factors 1. Several reviews have discussed how diet and nutrition contribute to human cancer risk 2-6 by affecting the initiation, promotion and progression of cancers 7-9. Two main types of dietary restriction are chronic calorie restriction (CCR) and intermittent calorie restriction (ICR) (e.g., intermittent fasting, alternate-day fasting, or routine periodic fasting) 10-13. Two population-based studies have found a linear and inverse association between CCR and breast cancer risk 14,15. However, because CCR requires constant food restriction, the tolerance and compliance for fasting is unsatisfactory; therefore, the effect of CCR might not be as good as expected. Researchers have been looking for more feasible styles of calorie restriction (CR) with comparable or even superior results. Currently, ICR regimens have been found to be equivalent to, if not better than, CCR for weight loss, providing an alternative approach for weight loss that might be better suited to some individuals 16. Several population studies have shown that ICR can improve indicators of chronic diseases (e.g., insulin sensitivity, high density lipoprotein cholesterol and fat oxidation) 17-19. The question of whether ICR show better tumor inhibitory effects than CCR remains unanswered. Unfortunately, most research focuses on animal models. There is little evidence from human studies.
Nutrition modulation of human aging: The calorie restriction paradigm
Molecular and cellular endocrinology, 2017
Globally, the aging population is growing rapidly, creating an urgent need to attenuate age-related health conditions, including metabolic disease and disability. A promising strategy for healthy aging based on consistently positive results from studies with a variety of species, including non-human primates (NHP), is calorie restriction (CR), or the restriction of energy intake while maintaining intake of essential nutrients. The burgeoning evidence for this approach in humans is reviewed and the major study to date to address this question, CALERIE (Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy), is described. CALERIE findings indicate the feasibility of CR in non-obese humans, confirm observations in NHP, and are consistent with improvements in disease risk reduction and potential anti-aging effects. Finally, the mechanisms of CR in humans are reviewed which sums up the fact that evolutionarily conserved mechanisms mediate the anti-aging effects o...
Caloric restriction, body fat and ageing in experimental models
Obesity Reviews, 2004
Summary Caloric restriction in animal models delays many age-related pathological condi- tions. Ageing rats have characteristically increased body weight, fat mass and a specific body fat distribution. This report will focus on the potential cause-effect relationship between increased fat mass and accelerated ageing. In humans, increased fat mass (obesity), and in particular increases in abdominal obesity as a result of
Caloric restriction and the aging process: a critique
The main objective of this review is to provide an appraisal of the current status of the relationship between energy intake and the life span of animals. The concept that a reduction in food intake, or caloric restriction (CR), retards the aging process, delays the age-associated decline in physiological fitness, and extends the life span of organisms of diverse phylogenetic groups is one of the leading paradigms in gerontology. However, emerging evidence disputes some of the primary tenets of this conception. One disparity is that the CR-related increase in longevity is not universal and may not even be shared among different strains of the same species. A further misgiving is that the control animals, fed ad libitum (AL), become overweight and prone to early onset of diseases and death, and thus may not be the ideal control animals for studies concerned with comparisons of longevity. Reexamination of body weight and longevity data from a study involving over 60,000 mice and rats, conducted by a National Institute on Aging-sponsored project, suggests that CR-related increase in life span of specific genotypes is directly related to the gain in body weight under the AL feeding regimen. Additionally, CR in mammals and " dietary restriction " in organisms such as Drosophila are dissimilar phenomena, albeit they are often presented to be the very same. The latter involves a reduction in yeast rather than caloric intake, which is inconsistent with the notion of a common, conserved mechanism of CR action in different species. Although specific mechanisms by which CR affects longevity are not well understood, existing evidence supports the view that CR increases the life span of those particular genotypes that develop energy imbalance owing to AL feeding. In such groups, CR lowers body temperature, rate of metabolism, and oxidant production and retards the age-related pro-oxidizing shift in the redox state.
Temporal linkage between the phenotypic and genomic responses to caloric restriction
Proceedings of the National Academy of Sciences, 2004
Caloric restriction (CR), the consumption of fewer calories while avoiding malnutrition, decelerates the rate of aging and the development of age-related diseases. CR has been viewed as less effective in older animals and as acting incrementally to slow or prevent age-related changes in gene expression. Here we demonstrate that CR initiated in 19-month-old mice begins within 2 months to increase the mean time to death by 42% and increase mean and maximum lifespans by 4.7 (P ؍ 0.000017) and 6.0 months (P ؍ 0.000056), respectively. The rate of age-associated mortality was decreased 3.1-fold. Between the first and second breakpoints in the CR survival curve (between 21 and 31 months of age), tumors as a cause of death decreased from 80% to 67% (P ؍ 0.012). Genome-wide microarray analysis of hepatic RNA from old control mice switched to CR for 2, 4, and 8 weeks showed a rapid and progressive shift toward the gene expression profile produced by long-term CR. This shift took place in the time frame required to induce the health and longevity effects of CR. Shifting from long-term CR to a control diet, which returns animals to the control rate of aging, reversed 90% of the gene expression effects of long-term CR within 8 weeks. These results suggest a cause-and-effect relationship between the rate of aging and the CR-associated gene expression biomarkers. Therefore, therapeutics mimicking the gene-expression biomarkers of CR may reproduce its physiological effects.
Nutrients, 2019
This review focuses on mechanisms of calorie restriction (CR), particularly the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis as an evolutionary conserved signal that regulates aging and lifespan, underlying the effects of CR in mammals. Topics include (1) the relation of the GH-IGF-1 signal with chronic low-level inflammation as one of the possible causative factors of aging, that is, inflammaging, (2) the isoform specificity of the forkhead box protein O (FoxO) transcription factors in CR-mediated regulation of cancer and lifespan, (3) the role for FoxO1 in the tumor-inhibiting effect of CR, (4) pleiotropic roles for FoxO1 in the regulation of disorders, and (5) sirtuin (Sirt) as a molecule upstream of FoxO. From the evolutionary view, the necessity of neuropeptide Y (Npy) for the effects of CR and the pleiotropic roles for Npy in life stages are also emphasized. Genes for mediating the effects of CR and regulating aging are context-dependent, particularly dependin...
Validated biomarkers of caloric restriction in rats: Markers of disease risk in humans?
Laboratory Rodents: Laboratory Rodents: Low calorie diets increase longevity Low calorie diets increase longevity and delay morbidity and delay morbidity Caloric Restriction (CR) Caloric Restriction (CR) CR is an experimental paradigm in CR is an experimental paradigm in which the dietary/caloric intake of a which the dietary/caloric intake of a group of animals is reduced relative to group of animals is reduced relative to that eaten by that eaten by ad libitum ad libitum fed controls fed controls Caloric restriction is the most potent, Caloric restriction is the most potent, most robust, and most reproducible most robust, and most reproducible known means of reducing morbidity known means of reducing morbidity and mortality in mammals and mortality in mammals How do we study complex How do we study complex biological/clinical problems? biological/clinical problems? How do we address such questions in How do we address such questions in humans, where our ability to manipulate humans, where our ability to manipulate and analyze the system is limited? and analyze the system is limited? Analytical Stability Analytical Stability Biologic Variability Biologic Variability AvA AvA AL AL vs vs DR DR Biological Biological vs vs Analytical Analytical In Rats: In Rats: Biological variability 5 fold greater than analytical variabi Biological variability 5 fold greater than analytical variability lity Analytical variability does not influence biological variabil Analytical variability does not influence biological variability ity