Studies of C57BL/6 mice are often restricted to one sex, with limited characterization of pathology as a function of age. As part of the National Institute on Aging/National Center for Toxicological Research Collaboration on Biomarkers, over 3000 males and 1500 females of this strain were raised, maintained, and used to evaluate longevity under specific pathogen-free conditions. A diet commonly used in testing the impact of agents was fed ad libitum or was restricted to 60% of normal consumption, starting when the mice were 14-16 weeks of age. Cardiac, renal, and central nervous system pathologies were significantly inhibited by dietary restriction (DR), as were bone degeneration, inflammation, hyperplasia, amyloid induction, and atrophy of secretory organs. Hematological disorders and tumors were among the most common problem in this strain, and they were ameliorated by DR. In males, for other neoplasms, adrenal adenomas, liver tumors, and hemangiomas combined with hemangiosarcomas were decreased by DR, variably in onset and progression. In females, DR decreased pituitary tumors, mammary tumors, and alveolar carcinomas, again variably in onset and progression.
A variety of physiological and behavioral parameters which relate to metabolism were continuously monitored in 18 month old female Fischer 344 rats which were maintained on either ad libitum or reduced calorie diets. Caloric restriction (CR) stimulated average motor activity per day, the duration of each feeding episode, food consumed per episode, and water consumed per gram lean body mass (LBM). However, CR limited total food consumption, feeding time, number of feeding episodes per day, total eating and drinking time, and the daily ratio of food consumed to water consumed, CR also decreased average body temperature per day, O2 consumption, CO2 production, and respiratory quotient. A variety of parameters concerning water consumption were not affected. CR rats ate their food immediately when food was presented during the light span, while ad libitum fed animals ate numerous small meals throughout the entire dark span. An anticipatory response to restricted feeding was also noted. Total motor activity, metabolism, and body temperature increased just prior to scheduled feeding and reached maximum values shortly after feeding, suggesting that these parameters were highly synchronized to feeding. Females and males were found to respond to caloric restriction in a similar fashion. Dramatic changes in respiratory quotient and body temperature suggest rapid shifts between metabolic pathways (glycolysis to gluconeogenesis) to obtain optimal efficiency. Lower body temperature and metabolism may provide protection against DNA damage, thereby increasing the survival potential of restricted rats. These responses may provide insight into the mechanisms by which caloric restriction acts to extend life span.
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