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Biomedical subjects

C L Goodrick

Publications and source records attributed to C L Goodrick.

At least 19 recordsLinked to original sources

Effects of intermittent feeding upon body weight and lifespan in inbred mice: interaction of genotype and age.

Beginning at either 1.5, 6 or 10 months of age, male mice from the A/J and C57BL/6J strains and their F1 hybrid, B6AF1/J were fed a diet (4.2 kcal/g) either ad libitum every day or in a restricted fashion by ad libitum feeding every other day. Relative to estimates for ad libitum controls, the body weights of the intermittently-fed restricted C57BL/6J and hybrid mice were reduced and mean and maximum life span were incremented when the every-other-day regimen was initiated at 1.5 or 6 months of age. When every-other-day feeding was introduced at 10 months of age, again both these genotypes lost body weight relative to controls; however, mean life span was not significantly affected although maximum life span was increased. Among A/J mice, intermittent feeding did not reduce body weight relative to ad libitum controls when introduced at 1.5 or 10 months of age; however, this treatment did increase mean and maximum life span when begun at 1.5 months, while it decreased mean and maximum life span when begun at 10 months. When restricted feeding was introduced to this genotype at 6 months of age, body weight reduction compared to control values was apparent at some ages, but the treatment had no significant effects on mean or maximum life span. These results illustrate that the effects of particular regimens of dietary restriction on body weight and life span are greatly dependent upon the genotype and age of initiation. Moreover, when examining the relationship of body weight to life span both between and within the various groups, it was clear that the complexity of this relationship made it difficult to predict that lower body weight would induce life span increment.

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Effects of intermittent feeding upon growth, activity, and lifespan in rats allowed voluntary exercise.

From weaning until death, male Wistar rats were housed in activity-wheel cages with one group maintained on an ad libitum (AL) diet and another provided the diet every-other-day (EOD). EOD-fed rats had a mean lifespan of 124 weeks compared to 103 weeks for AL-fed rats. While post-weaning body weight and growth rates were reduced among the EOD-fed animals compared to AL-fed animals, there was no significant difference in growth duration. Positive correlations were observed between lifespan and estimates of growth rate and duration in the AL group but not in the EOD group; thus, little evidence was produced to support the hypothesis that growth rate is inversely related to longevity. While the EOD feeding regimen resulted in higher activity levels later in life, wheel activity levels were actually lower in this group in early life compared to the AL group. The observation of reduced wheel activity among young rats fed EOD was replicated in a second experiment. Thus, little support was obtained for the hypothesis that increased activity mediates the beneficial effects of dietary restriction on longevity, unless this mechanism is active late in the lifespan.

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Differential effects of intermittent feeding and voluntary exercise on body weight and lifespan in adult rats.

Male wistar rats were housed in laboratory cages or activity-wheel cages at eight 10.5 or 18 months of age. Part of each cage group continued to be fed ad libitum, whereas the remaining animals were fed every other day. Compared with the ad libitum condition, intermittent feeding decreased body weight and increased lifespan at both ages in both caging conditions. Compared with the caged condition, voluntary exercise in activity wheels reduced body weight only in the 10.5-month-old group fed ad libitum but produced no effect on survival of either age group. The results suggest that intermittent feeding can enhance survival in mature rats even beyond ages at which body weight growth usually ceases, whereas voluntary exercise appears to have an early threshold beyond which increases in longevity are not observed.

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Decreased resistance to extinction in ob/ob mice following operant training.

Inconsistent results have emerged from past studies in which operant conditioning paradigms were used to assess the hunger motivation of genetically obese mice relative to that of normal mice. Methodological considerations indicated the need to examine operant performance to a criterion, rather than performance during time-based sessions, and then to focus upon response differences in resistance to extinction. Therefore, genetically obese (ob/ob) mice and normal littermates were trained successfully to bar-press for 100 food rewards on either a CRF or a FR-10 schedule of reinforcement. Extinction behavior was then examined over 9 daily 1-hr sessions. While obese and normal mice evidenced similar patterns of learning, or response discrimination for food rewards, they evidenced different levels of hunger motivation during extinction conditions. Obese mice displayed a greater reduction in responding across extinction sessions, or less resistance to extinction, than normal mice following training on both schedules of reinforcement. These findings suggest that ob/ob mice exhibit lower levels of hunger motivation than normal littermates.

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Relationship of sex, exercise, and growth rate of life span in the Wistar rat: a multivariate correlational approach.

Measures of body weight change were calculated and examined in relation to the life span of 68 male and 71 female Wistar rats that were maintained either in wheel-cage units of cages without wheels. The analysis revealed the following: (a) sex and wheel exercise accounted for nearly one third of the obtained variation in life span; (b) growth rate, defined as the ratio of peak body weight to growth duration, accounted for over 15% of the variance in life span unattributable to sex and exercise; (c) measures of body weight gain early in the developmental span were virtually unrelated to life span; (d) beyond 9 months of age, measures of body weight gain showed a significant positive relationship with life span. Thus, there was no evidence of a negative relationship between life span and body weight gain during early life.

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Effects of intermittent feeding upon growth and life span in rats.

From weaning to death, 28 male Wistar rats were maintained on an ad libitum (AL) diet, and 24 counterparts were provided the diet every-other-day (EOD). The mean life span of the EOD group represented an 83% increase over that of the AL group. Furthermore, a Gompertzian analysis of mortality rates suggested that the rate of aging was retarded in the EOD group. While body weight and growth rate were reduced in the EOD group, their growth duration was 75% longer compared to the AL group. Significant positive relationships emerged between life span and growth rate parameters in the AL group; however, no significant relationships were found between life span and body weight parameters in the EOD group. Therefore, in support of the hypothesis that dietary restriction effects prolongevity through retarded development, evidence was produced only in the between-group comparisons of AL- and EOD-fed animals.

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Differential effects of age on motor performance in two mouse strains.

The performance of male A/J and C57BL/6J mice from three age groups (4, 18, and 24 months) was observed in a battery of tests designed to assess age-related impairments in motor abilities. A/J mice were superior to C57BL/6J mice in tasks requiring upper body strength, such as tests of grip strength and tightrope performance. C57BL/6J mice were superior performers in tasks requiring balance and coordination, such as movement on stationary and rotating rods. In addition, the C57BL/6J strain generally exhibited greater locomotor activity, such as measured in open field and wheel-running tests. Significant age-related deficits were observe among A/J mice in tests of grip strength, balance rod, rotorod, and wheel activity; and among C57BL/6J mice, in balance, rod, tightrope, exploratory activity, and wheel activity tests. Except for scores of exploratory activity (free versus forced exploration), the test measures tended to be uncorrelated; however, the degree and magnitude of intercorrelation among test scores increased with age. The results underscore the need to consider genotype in the assessment of age-related motor impairments in animal models.

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Age and neurochemical correlates of radial maze performance in rats.

Young adult (8 months) and aged (26 months) female Wister rats were tested in a 12-arm radial maze in which the optimal strategy was to enter all arms without a repetition. In order to determine if possible age-associated alterations in behavior were correlated with defects in cholinergic. GABAergic and adrenergic neurons in the hippocampus and cerebral cortex, the activities of choline acetyltransferase (CAT), glutamic acid decarboxylase (GAD) and tyrosine hydroxylase (TH) were assayed in these regions of all animals after testing in the radial maze. In the maze, the aged rats continued to perform at the chance level after 15 trials, whereas the young rats had virtually mastered the task. The only significant neurochemical age effect was an increase in hippocampal TH. However, analysis of individual differences among rats revealed positive correlations between maze performance and hippocampal CAT in the aged group and cortical GAD in both the young and aged groups.

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Effects of long-term voluntary wheel exercise on male and female Wistar rats. I. Longevity, body weight, and metabolic rate.

Male and female Wistar rats (n = 140) age 1.5 months were maintained in either wheel-cage units or cage units for their entire life span. Voluntary wheel exercise significantly increased the mean longevity of both male and female rats compared with that of control rats. Between and within groups, growth duration was positively related to longevity, and growth rate was negatively related to longevity. These factors may explain differences in longevity between exercise and control groups and differences in longevity between male and female groups. These factors of growth, here defined in terms of body weight increment, may possibly account for many instances of group differences in longevity.

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Body weight increment and length of life: the effect of genetic constitution and dietary protein.

Groups of inbred A/J and C57BL/6J mice and hybrid F1 mice were fed low dietary protein (4% casein) or normal dietary protein (26% casein), with 50 mice in each of the six subgroups. For individual mice within subgroups, growth rate was negatively related to longevity; i.e., the slower the rate of growth the greater the life-span. Between subgroups, the longer the mean growth duration, the longer the mean lifespan. Positive relationships were obtained within subgroups for peak body weight and longevity. It is concluded that, for mice, slowing the rate of growth and increasing growth duration results in a significant increase in the life-span, and the life-span increment is not related to high peak body weight since high body weight, per se, was not correlated with life-span.

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Body weight change over the life span and longevity for C57BL/6J mice and mutations which differ in maximal body weight.

Body weights were obtained monthly for mutant groups with the C57BL/6J genetic background which differ in body weight (bg, c,J Ay, ob), and for a control group (C57BL/6J) (n = 16, N = 80). The mean longevity was significantly lower for all mutant groups compared with the mean longevity of the control group. Although obese mice (ob) had a shorter life span than other mutant groups, mice which also attained a very high body weight (yellow, Ay) did not differ significantly in longevity from thin mutant mice. Moreover, peak body weight was positively correlated with longevity for all mouse groups. All mouse groups showed a terminal decline in body weight except the albino group which gained weight throughout life. In general, long-lived mice obtained a greater terminal weight loss than short-lived mice within groups. The major finding of this study was that within each group there was a negative relationship obtained between growth rate and longevity.

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Adaptation to novel environments by the rat: effects of age, stimulus intensity, group testing, and temperature.

Adaptation of operant bar pressing in a dark 2-bar test box was determined during 2-hr tests for singly tested rats 16-18, 24-32, and 750-800 days old. Rats 16-18 days old failed to adapt during the test, although all other age groups did. Adaptation occurred more slowly for the 120-150 day-old group than for the remaining 2 age groups. Experiments with the 2 youngest groups showed that bright light lowered response levels of both age groups, compared with controls, but failed to alter the course of adaptation. In contrast, group testing resulted in lowered response levels and faster adaptation for 16-18 day-old rats, but higher response levels for 24-32 day-old rats compared with singly tested controls. High temperature (32.5 degrees C) resulted in adaptation for the 2 younger groups. The failure of 16-18 day-old rats to adapt may have been due to lower body temperature while in the test chamber than while in the home cage nest area.

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Voluntary exposure to light by young and aged albino and pigmented inbred mice as a function of light intensity.

Young (5 month) and old mice (23 and 26 months) of the inbred A/J and C5BL/6J strains (N = 80) were isolated in ventilation chambers with ad lib food and water for 1 week at a time. Each animal was allowed to select its own lighting schedule by pressing one lever to turn on a light of either 10.76 or 166.40 lux illumination and pressing another lever to turn the light off. Three-way analyses of variance for Age, Strain, and Illumination effects on parameters of bar pressing, stimulus change, and light duration patterns per circadian period (24 hr) indicate that old mice are less active than young mice and the A/J mice are less active than C57BL/6J mice. Young mice spent more time in the dark than old mice and the A/J albino mice spent more time in the dark than did the C57BL/6J pigmented mice. Other age and strain differences were noted as well and are discussed with respect to some theories of light exposure by nocturnal animals.

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