Charles L. Goodrick

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.

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.

Effects of Long-Term Voluntary Wheel Exercise on Male and Female Wistar Rats

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 long

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.

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.

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.

Behavioral differences in young and aged mice: Strain differences for activity measures, operant learning, sensory discrimination, and alcohol preference

Young and aged mice of the A/J and C57BL/6J inbred strains were given a series of behavioral tests which measured activity of various kinds, emotionally, operant learning, sensory discrimination, and alcohol preference. In general, compared with young mice, aged mice were less active, similar in emotionally, learned the operant discrimination as well, but extinguished more slowly, had poorer discrimination for sweet and bitter taste stimuli, and preferred alcohol to a lesser degree. Strain differences were obtained for most of these tests, and age-strain interactions occurred frequently indicating that behavioral changes occur at different rates for groups which differ in genetic constitution.

Effects of lifelong restricted feeding on complex maze performance in rats

Male Wistar rats reared on a regimen of every-other-day (EOD) feeding (24% protein) since weaning were compared in complex maze learning at 30 mo of age to young (6 mo) and old (22 mo) ad libitum (AL) fed groups. Maze learning performance for the aged, EOD-fed group was equivalent to that of young AL-fed rats, and superior to that of aged AL-fed rats.

EXPLORATION OF NONDEPRIVED MALE SPRAGUE-DAWLEY RATS AS A FUNCTION OF AGE

Groups of male Sprague-Dawley rats 31 to 730 days old were placed in an open field and scores were obtained of ‘exploratory’ and ‘nonexploratory’ responses. Young recently weaned rats (31-day-old) and young-mature rats (94-day-old) had high scores of exploration responses and low scores of nonexploration responses in comparison with adolescent rats (52 or 73 days old) or older rats (365 or 730 days old). After reaching maturity (94 days old), exploration decreased with increasing age.

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.