Adaptive role of caloric intake on the degenerative disease processes

• Published in: Toxicological sciences 1999-12, Vol.52 (2), p.3-12
• Main Authors: HART, R. W, DIXIT, R, PIPKIN, J, LI, S. Y, SENG, J, TURTURRO, A, LEAKEY, J. E. A, FEUERS, R, DUFFY, P, BUFFINGTON, C, COWAN, G, LEWIS, S
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological; Aging - physiology; Animals; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Disease - etiology; Energy Intake - physiology; Foods and miscellaneous; Homeostasis - physiology; Humans; Longevity; Medical sciences; Neoplasms - etiology; Neoplasms - physiopathology; Oxidative Stress; Stress, Physiological - physiopathology; Tumors
• ISSN: 1096-6080; 1096-0929; 1096-0929
• DOI: 10.1093/toxsci/52.2.3

Carcinogenicity and aging are characterized by a set of complex endpoints, which appear as a series of molecular events. Many of these events can be modified by caloric intake. Since most of these processes determine an organism's ability to cope with various environmental stressors, it is not surprising that a relationship (in the presence of a constant nutrient density) exists between caloric intake and time-to-tumor and/or life span. Our studies have clearly shown that generally, the greater the caloric intake, the greater the body weight, the higher the incidence of spontaneous tumor occurrence, the greater the susceptibility to chemical carcinogens, and the shorter the life span. It is also recognized that variables other than body weight influence the life span and carcinogenesis. We have focused our attention on the questions of how and to what extent caloric intake modifies those homeostatic processes believed to be critical in determining the ability of an organism to cope with endogenous and exogenous stresses such as chemical, physical, and biological carcinogens. The response of an organism to its environment can be divided into four categories--physiological, metabolic, molecular, and cellular. We have found that, from a physiological perspective, decreasing caloric intake causes body temperature in rodents to be decreased by 0.5 to 1.8 degrees C and water consumption to be increased by 80%, as is running activity. However, metabolic output per gram of lean body mass is not altered. Reproductive capacity declines, whereas the ECG waveform is preserved as caloric intake decreases. Alterations in these and other physiological functions suggests that energy intake serves as a signal to up-regulate or down-regulate functions related to the flight-or-fight response observed in placental mammals. A number of key metabolic pathways are altered as a function of lowered caloric intake, even though the rate of food consumption per gram of lean body mass remains steady during body weight decreases caused by decreasing caloric intake. Pharmacological compartmentalization, however, is altered. As caloric intake declines, changes occur in the expression of a number of drug-metabolizing enzymes, with the most striking effect seen in sex-specific growth hormones and liver-dependent phase I and phase II enzymes. Additionally, oxidative stress (free-radical and mediated damage to macromolecules) appears to decrease as a function of reduced caloric intake. A num