Energy metabolism and aging: a lifelong study of Fischer 344 rats

1992 ◽  
Vol 263 (3) ◽  
pp. E448-E452 ◽  
Author(s):  
R. J. McCarter ◽  
J. Palmer

Metabolic rate is widely regarded as an important component of aging processes, but variation of metabolic rate with age has not been well characterized. The purpose of the present study was to measure daily metabolic rate under usual living conditions over the lifespan of barrier-maintained Fischer 344 rats. In addition, effects of life-prolonging food restriction were assessed. Metabolic rate was measured indirectly by analysis of gas entering and leaving standard rodent cages over a 24-h period. Group A rats were fed ad libitum. Group B rats were fed 60% of ad libitum intake from 6 wk of age. Both group A and group B rats exhibited variation of metabolic rate per unit lean mass over the lifespan, with metabolic rate decreasing from 6 to 18 mo and then increasing from 18 to 24 mo of age. Results show estimates of lifetime energy expenditure in rats should take account of variability of metabolic rate and confirm the life-prolonging action of food restriction is not a consequence of reduced metabolic rate per unit metabolic mass. Rather, restricted rats are able to sustain appropriate fluxes of nutrients and appropriate metabolic rate under conditions of fuel utilization which promote maintenance of cellular homeostasis.

1982 ◽  
Vol 242 (1) ◽  
pp. R89-R93 ◽  
Author(s):  
R. J. McCarter ◽  
E. J. Masoro ◽  
B. P. Yu

Age changes in oxygen consumption and the structural composition of the lateral omohyoideus muscle were studied in adult male rats. The rate were either fed ad libitum (group A) or 60% of the ad libitum intake (group R). An age-related loss in muscle mass did not occur even at advanced ages in group A or group R rats. Muscle fiber diameter decreased with age in both groups but a concomitant increase in the number of fibers prevented a change in muscle mass. The muscles of group R rats contained the same number of fibers as those of group A rats at all ages. The muscles of group A rats showed a progressive loss in rate of resting oxygen consumption until 18 mo of age. A similar but less marked loss in oxygen consumption occurred in the muscles of group R rats. These results provide further evidence that life-prolonging food restriction modulates physiological changes associated with the aging process.


1999 ◽  
Vol 86 (2) ◽  
pp. 617-622 ◽  
Author(s):  
Terence H. Risby ◽  
Long Jiang ◽  
Sigfried Stoll ◽  
Donald Ingram ◽  
Edward Spangler ◽  
...  

Breath ethane, O2consumption, and CO2 production were analyzed in 24-mo-old female Fischer 344 rats that had been fed continuously ad libitum (AL) or restricted 30% of AL level (DR) diets since 6 wk of age. Rats were placed in a glass chamber that was first flushed with air, then with a gas mixture containing 12% O2. After equilibration, a sample of the outflow was collected in gas sampling bags for subsequent analyses of ethane and CO2. The O2 and CO2 levels were also directly monitored in the outflow of the chamber. O2 consumption and CO2 production increased for DR rats. Hypoxia decreased O2consumption and CO2 production for the AL-fed and DR rats. These changes reflect changes in metabolic rate due to diet and [Formula: see text]. A significant decrease in ethane generation was found in DR rats compared with AL-fed rats. Under normoxic conditions, breath ethane decreased from 2.20 to 1.61 pmol ethane/ml CO2. During hypoxia the levels of ethane generation increased, resulting in a DR-associated decrease in ethane from 2.60 to 1.90 pmol ethane/ml CO2. These results support the hypothesis that DR reduces the level of oxidative stress.


1989 ◽  
Vol 257 (2) ◽  
pp. E175-E179 ◽  
Author(s):  
R. J. McCarter ◽  
J. R. McGee

It is widely held that restriction of food intake leads to a decrease in metabolic rate, and this effect has been implicated as the mechanism by which food restriction retards aging in laboratory rodents. Data on which this belief is based were obtained mostly from studies of basal metabolic rate after acute rather than chronic food restriction. In contrast we previously reported no effect of chronic food restriction on metabolic rate measured under usual living conditions. The present study examines changes in metabolic rate immediately after restriction of food so as to include the initial response to decreased intake of food. Two groups of specific pathogen-free Fischer 344 rats were housed under barrier conditions from 6 to 24 wk of age. Restricted rats were fed 60% of food consumed by rats eating ad libitum. Metabolic rate was measured indirectly by gas analysis with rats under normal daily living conditions (24MR) and basal metabolic rate (BMR) was also measured. Both 24MR and BMR decreased after food restriction, but this decrease was transient, so that within a few weeks metabolic rate of restricted rats was the same as that of rats fed ad libitum.


2002 ◽  
Vol 2002 (37) ◽  
Author(s):  
Byung Pal Yu ◽  
Edward J. Masoro ◽  
Ikuo Murata ◽  
Helen A. Bertrand ◽  
Frederick T. Lynd

A life-span study was carried out on longevity, pathologic lesions, growth, lean body mass, and selected aspects of muscle of barrier-maintained SPF Fischer 344 rats fed either ad libitum (Group A) or 60% of the ad libitum intake (Group R). Food restriction was as effective in prolonging the life of already long-lived SPF rats as previously shown for rats maintained in conventional facilities. Food restriction not only increased the mean length of life but also acted to extend life-span since more than 60% of the Group R rats lived longer than the longest lived Group A rat. Renal lesions occurred at an earlier age in Group A rats than in Group R rats and progressed more rapidly. Death of most Group A rats was associated with severe renal lesions while few Group R rats showed such lesions at death. Food restriction was also found to delay or prevent interstitial cell tumors of the testes, bile duct hyperplasia, myocardial fibrosis and myocardial degeneration. Gastrocnemius muscle mass declined in advanced age and food restriction delayed this decline. Interestingly, however, lean body mass did not progressively decline with increasing age but rather decline occurred only after the onset of the terminal disease process. Copyright (c) The Gerontological Society of America. Reproduced by permission of the publisher. Byung Pal Yu, Edward J. Masoro, Ikuo Murata, Helen A. Bertrand, Frederick T. Lynd, Life Span Study of SPF Fischer 344 Male Rats Fed Ad Libitum or Restricted Diets: Longevity, Growth, Lean Body Mass and Disease. J. Gerontol. 37 , 130-141 (1982).


2006 ◽  
Vol 21 (3) ◽  
pp. 168-176 ◽  
Author(s):  
Míriam Elias Cavallini ◽  
Nelson Adami Andreollo ◽  
Konradin Metze ◽  
Marina Raquel Araújo

PURPOSE: To evaluate and to compare macro and microscopically the intense injuries of the gastric mucosa of rats which were caused by NSAIDS celecoxib and indomethacin and the gastric cytoprotection with omeprazole and misoprostol. METHODS: The sample is formed by one hundred and fifty Wistar rats with average weight 200 g, distributed in four groups, such as: Group A, subdivided in groups A1 and A2 - pre-treatment with omeprazole (20 mg/rat) during seven days and on the 8th day - use of NSAIDS, concerning A1 (20 rats) were given celecoxib (1mg/rat) and A2 (20 rats) were given indomethacin. The Group B, subdivided in group B1 and B2 - pre-treatment with misoprostol (20mg/rat) during seven days and on the 8th day use of NSAIDS, concerning B1 (20 rats) were given celecoxib (1 mg/ rat) and B2 (20 rats) were given indomethacin (12.5 mg/rat). The Group C: were not given cytoprotection during seven days, from the 7th to the 8th day - fast of food and water ad libitum, on the 8th day of NSAIDS use, concerning C1 (20 rats) were given celecoxib, C2 (20 rats) were given indomethacin (12.5 mg/ rat), C3 (20 rats) were given celecoxib (200mg/rato), and Group D - control group, concerning 10 rats were observed during seven days ingesting food and water ad libitum. On the 9th day, the stomachs were taken out and were macro and microscopically evaluated for the identification of the gastric injuries. RESULTS: On the macroscopic studies, the groups A2, B2 and C2 presented a remarkable high number of injuries for cm² /animal, respectively 18.55 injuries for cm² /animal, 16.25 injuries for cm² /animal and 13.55 injuries for cm²/animal. On the microscopic studies, the percentage of the injured mucosa, presented expressive difference among the groups A1, B1, C1 when compared to the groups A2, B2, C2 (p<0.0001). The average of the length/injury and the average of the depth of the injuries did not present expressive statistics differences among the groups A2, B2 and C2. The average of the edema presented expressive statistics difference among the groups A2 and D; B2 and C2 and between C2 and D (p < 0.05). CONCLUSIONS: The indomethacin on the applied concentration causes a great number of macroscopic and microscopic injuries to gastric mucosa of rats when compared to celecoxib which does not cause lesions. Omeprazole and misoprostol on the applied concentrations do not present macroscopic and microscopic effectiveness on the gastric cytoprotection when applying indomethacin. Considering the microscopic analysis of the average of the edema, the group of animals, which was given misoprostol as cytoprotection, presented a lower average compared to the group which was given omeprazole.


1994 ◽  
Vol 266 (6) ◽  
pp. E946-E952 ◽  
Author(s):  
G. D. Cartee ◽  
D. J. Dean

The time course (1, 5, or 20 days) for the effect of dietary restriction (DR; approximately 25% reduction below ad libitum intake) on epitrochlearis and flexor digitorum brevis (FDB) muscle glucose transport activity was studied in female Fischer 344 rats (8 mo old). Epitrochlearis glucose transport activity with 100 microU/ml insulin was increased by 38% after 5 days of DR (P < 0.05) despite no change in glucose transport activity with 0 or 20,000 microU/ml insulin. The increase with 100 microU/ml insulin was not further enhanced by 20 days of DR. DR did not result in a significant increase in the glucose transport activity of the FDB with 0, 100, or 20,000 microU/ml insulin. Abdominal fat content was significantly (P < 0.01) reduced below ad libitum levels only after 20 days of DR. These results demonstrate that DR-induced improvement in epitrochlearis glucose transport activity with a physiological insulin concentration can occur very rapidly, preceding detectable changes in basal or maximal insulin-stimulated glucose transport activity or abdominal fat pad mass, and the enhancement of insulin action does not occur simultaneously in all muscles.


1995 ◽  
Vol 32 (4) ◽  
pp. 419-422 ◽  
Author(s):  
J. D. Thurman ◽  
J. R. Hailey ◽  
A. Turturro ◽  
D. W. Gaylor

Two of 632 Fischer-344 rats in a food restriction study had spontaneous, bilateral, multicentric renal tubular cell carcinomas. Although there were 104 litters represented in this study, both rats that developed this rare neoplasm were from the same litter. The littermates, one male and one female, were in the food-restricted treatment groups (60% of ad libitum intake) and were 550 and 447 days old, respectively, at death. The probability that the two rare bilateral renal neoplasms occurred by a chance event in littermates is approximately 0.8%. The apparent familial predisposition for development of specific types of neoplasms emphasizes the importance of randomization of individuals into treatment groups and consideration of lineage for rare tumors.


2011 ◽  
Vol 39 (01) ◽  
pp. 135-144 ◽  
Author(s):  
Guowei Zhang ◽  
Xing Zeng ◽  
Caixia Li ◽  
Jijun Li ◽  
Yu Huang ◽  
...  

The study aimed to evaluate inhibition effect of sclerotia of Polyporus umbellatus Fries aqueous extract (SPUE) and polyporus polysaccharide (PPS) on bladder cancer, then to measure their effect on mRNA expression of glutathione S-transferase π (GSTPi) and NAD(P)H:quinone oxidoreductase 1 (NQO1) in female Fischer-344 rats model. The model rats were induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) for a period of 8 weeks and saccharin for 12 weeks. SPUE (50 mg/kg, 250 mg/kg, 500 mg/kg) and PPS (28 mg/kg) were orally administrated to the model rats during the whole study. Compared to the control group, a more preventive effect of SPUE and PPS treatment on bladder cancer was discovered, higher mRNA upregulation of GSTpi and NQO1 was seen in the treatment group. Furthermore, the GSTPi and NQO1 mRNA upregulated level in the low-dose group (SPUE 50 mg/kg) was at maximum. In brief, SPUE and PPS are highly effective in inhibiting bladder carcinogenesis in rats, which may be associated with upregulation of GSTPi and NQO1 in the bladder.


1990 ◽  
Vol 115 (2) ◽  
pp. 269-275 ◽  
Author(s):  
M. Morrison ◽  
R. M. Murray ◽  
A. N. Boniface

SUMMARYA feeding trial was performed during 1986, in Townsville, Australia, to describe alterations in nutrient metabolism, and the coincident gross changes in rumen microbiology, when a sulphurdeficient diet was supplemented with inorganic sulphur. Eight Merino sheep were fedad libituma spear grass (Heteropogon contortus) hay of low sulphur content (0·4 g/kg DM), supplemented with all other essential minerals. Upon supplementation, daily sulphur intake was increased toc.0·75 g and four animals continued to be fedad libitum(group A) whilst the remaining animals were restricted in feed intake (group B). Sulphur supplementation caused a twofold increase in the feed intake of group A (P< 0·05). In both groups of animals, sulphur supplementation increased the fermentation of cotton thread cellulose (P< 0·05), as well as of ground plant dry matter (P< 0·05), suspended in the rumen in nylon bags for 24 and 48 h. The apparent digestibility of organic matter (AOMD) was also increased by sulphur supplementation; from 30·6 to 39·3% in group A (P< 0·05) and from 35·1 to 41·5% in group B (P> 0·05). The difference in AOMD between groups with sulphur supplementation was not significant, despite group B maintaining a longer retention of fluid digesta in the rumen (20·7 v. 25·3 h) with a significantly lowered rumen volume (4·68 v 3·67 litres,P< 0·05) and outflow of fluid digesta from this site (5·31 v 3·58 litres/day,P< 0·05). Sulphur supplementation increased the molar proportion of acetic acid in rumen fluid (P< 0·05) but lowered propionic and butyric acids in group A (P< 0·05). Only the molar proportion of propionic acid in rumen fluid was significantly lowered in group B (P< 0·05). In both groups of animals, counts of fluid-borne rumen bacteria, protozoa and sporangia of rumen anaerobic fungi (RAF) all increased significantly with sulphur supplementation (P< 0·05 in all instances), but no significant differences were observed between groups in microbial counts, despite the different feeding regimes. The increase in sporangial forms of RAF was most marked; no sporangial forms were detectable until the diet was supplemented with sulphate and measurable concentrations of rumen sulphide were observed. This is the first account of nondetectable concentrations of RAF brought about by the nutritional status of the diet.


Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 263-269 ◽  
Author(s):  
Manuel D. Gahete ◽  
José Córdoba-Chacón ◽  
Raúl M. Luque ◽  
Rhonda D. Kineman

In mice, GH levels rise in response to short-term fasting or starvation (food restriction to 40% of ad libitum intake), similar to that which occurs in humans in response to fasting or anorexia. Recent studies using acyl-ghrelin knockout mice have suggested that the rise in GH during food restriction is essential to support glucose levels. To directly test this hypothesis, adult-onset isolated GH deficient (AOiGHD) mice and their GH-replete littermate controls were provided 40% of ad libitum food intake for 11 d. As previously shown, food restriction increased GH levels in controls, and this response was not observed in AOiGHD mice. In both controls and AOiGHD, food restriction resulted in an initial decline in glucose, which stabilized to 82–85% of ad libitum-fed values by d 2. In addition, loss of lean mass in response to food restriction was not altered by GH status. However, the loss of fat mass and the associated rise in circulating free fatty acids and ketones was blunted in starved AOiGHD mice compared with controls. Taken together, these results suggest a rise of GH during starvation is not required to support glucose levels and muscle mass but may be important in supporting fat mobilization.


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