Age-related Differences In Response Research Articles

The Effects of POWER Training in Young and Older Adults after Stroke.

Background. Approximately 35,000 strokes occur annually in adults below the age of 40, and there is disappointingly little data describing their responses to rehabilitation. The purpose of this analysis was to determine the effects of Poststroke Optimization of Walking using Explosive Resistance (POWER) training in young (<40 years) and older (>60 years) adults and to describe relationships between training-induced improvements in muscular and locomotor function. Methods. Data was analyzed from 16 individuals with chronic stroke who participated in 24 sessions of POWER training. Outcomes included muscle power generation, self-selected walking speed (SSWS), 6-minute walk test, Fugl-Meyer motor assessment, Berg Balance Scale, and Dynamic Gait Index. Results. There were no significant differences between groups at baseline. Within-group comparisons revealed significant improvements in paretic and nonparetic knee extensor muscle power generation in both groups. Additionally, young participants significantly improved SSWS. Improvements in SSWS were more strongly associated with improvements in power generation on both sides in young versus older participants. Conclusions. Younger adults after stroke seem to preferentially benefit from POWER training, particularly when increasing gait speed is a rehabilitation goal. Future research should aim to further understand age-related differences in response to training to provide optimal treatments for all individuals following stroke.

Age-Related Differences in Response to Music-Evoked Emotion Among Children and Adolescents with Autism Spectrum Disorders.

While research regarding emotion recognition in ASD has focused primarily on social cues, musical stimuli also elicit strong emotional responses. This study extends and expands the few previous studies of response to music in ASD, measuring both psychophysiological and behavioral responses in younger children (ages 8-11) as well as older adolescents (ages 16-18). Compared to controls, the ASD group demonstrated reduced skin conductance response to music-evoked emotion. Younger groups, regardless of diagnosis, showed greater physiological reactivity to scary stimuli than to other emotions. There was a significant interaction of age group and diagnostic group in identifying scary music stimuli, possibly evidencing disrupted developmental trajectories in ASD for integrating physiological and cognitive cues that may underlie symptoms of anxiety.

DNA double-strand break repair is impaired in presenescent Syrian hamster fibroblasts.

BackgroundStudies of DNA damage response are critical for the comprehensive understanding of age-related changes in cells, tissues and organisms. Syrian hamster cells halt proliferation and become presenescent after several passages in standard conditions of cultivation due to what is known as «culture stress». Using proliferating young and non-dividing presenescent cells in primary cultures of Syrian hamster fibroblasts, we defined their response to the action of radiomimetic drug bleomycin (BL) that induces DNA double-strand breaks (DSBs).ResultsThe effect of the drug was estimated by immunoblotting and immunofluorescence microscopy using the antibody to phosphorylated histone H2AX (gH2AX), which is generally accepted as a DSB marker. At all stages of the cell cycle, both presenescent and young cells demonstrated variability of the number of gH2AX foci per nucleus. gH2AX focus induction was found to be independent from BL-hydrolase expression. Some differences in DSB repair process between BL-treated young and presenescent Syrian hamster cells were observed: (1) the kinetics of gH2AX focus loss in G0 fibroblasts of young culture was faster than in cells that prematurely stopped dividing; (2) presenescent cells were characterized by a slower recruitment of DSB repair proteins 53BP1, phospho-DNA-PK and phospho-ATM to gH2AX focal sites, while the rate of phosphorylated ATM/ATR substrate accumulation was the same as that in young cells.ConclusionsOur results demonstrate an impairment of DSB repair in prematurely aged Syrian hamster fibroblasts in comparison with young fibroblasts, suggesting age-related differences in response to BL therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12867-015-0046-4) contains supplementary material, which is available to authorized users.

Poster #M14 USE OF FOLATE TO PREVENT SCHIZOPHRENIA IN ANIMAL MODEL OF KETAMINE INDUCE SCHIZOPHRENIA IN RATS

Acetylcholine (ACh) release is modulated pre-synaptically by both muscarinic and nicotinic receptor-mediated processes. While muscarinic autoreceptors inhibit ACh release, nicotinic autoreceptors enhance ACh release and thus disruption of these processes could potentially affect cholinergic toxicity following exposure to anticholinesterases. Marked age-related differences in sensitivity to some organophosphorus (OP) anticholinesterases have been reported. We compared nicotinic autoreceptor function (NAF) during maturation and aging and evaluated its potential modulation by the common OP insecticide, chlorpyrifos (CPF). Cortical synaptosomes were pre-loaded with [3H]choline, superfused (0.6 ml/min) with physiological buffer and [3H]ACh release was evoked with potassium (KCl, 9 mM), with or without co-addition of exogenous ACh to stimulate nicotinic autoreceptors. Fractions of perfusate were subsequently collected and area under the curve (AUC) for [3H] was analyzed by scintillation counting. The difference in evoked release due to co-addition of exogenous ACh was defined as NAF. Under these conditions, atropine (ATR, 0.1 μM) appeared requisite for NAF; thus this muscarinic antagonist was subsequently added to all perfusion buffers. In synaptosomes from adult tissues, exogenous ACh (3–100 μM) significantly increased release in a concentration-dependent manner. The nicotinic antagonist mecamylamine (MEC, 100 μM) substantially reduced the potassium-evoked release elicited by co-addition of ACh (10 μM). Interestingly, the nicotinic agonists nicotine (NIC) and dimethylphenylpiperazinium (DMPP; 0.1–10 μM) had no effect on release. The active metabolite of CPF (i.e. chlorpyrifos oxon (CPO), 1–10 μM) inhibited NAF in vitro. Maturation-related expression of NAF was noted (AUC with co-addition of 10 μM ACh: 7-day rats, 7±6; 21-day rats, 44±6; 90-day rats, 196±37; 24-month rats, 173±52). NAF was substantially reduced (67–91%) 96 h after maximum tolerated dosages of CPF in adult and aged rats (279 mg/kg, sc) but not in juveniles (127 mg/kg, sc), even though AChE inhibition was similar among the age groups (>80%). Together these data suggest that NAF is differentially expressed during maturation and that this neuromodulatory process may be selectively altered by some OP insecticides, potentially contributing to age-related differences in response to AChE inhibitors. As NAF has been postulated to be activated under conditions of ‘impaired’ cholinergic function, selective alteration of this pre-synaptic process by OP anticholinesterases may be also important in age-related conditions associated with cholinergic hypofunction.

Coronary artery disease and age: beyond atherosclerosis

Coronary artery disease and age: beyond atherosclerosis

Investigating age-related differences in responses to screening items for internalising disorders in three national surveys

BackgroundEpidemiological studies typically report lower prevalence of mental disorders among older adults relative to middle-aged and young adults. A possible explanation is that age-related bias in the screening items of diagnostic instruments leads to older adults being differentially screened out of the full assessment. This study investigated potential age-related bias in screening items for internalising disorders in three epidemiological surveys. MethodMeasurement invariance was estimated for the internalising disorder screening items in the 2007 and 1997 Australian National Survey of Mental Health and Wellbeing, and the 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions. These surveys assessed mental disorders using the Composite International Diagnostic Interview (CIDI) and the Alcohol Use Disorder and Associated Disabilities Interview Schedule–DSM-IV Version (AUDADIS-IV). A series of multi-group confirmatory factor analyses (CFA) were performed for each survey across older (65–85 years), middle (35–64 years) and young (16–34 years) adults. ResultsDifferences between successive CFA models for each survey were negligible, indicating measurement invariance across age groups for the CIDI and AUDADIS-IV screening items. LimitationsThe number of items and symptoms representing internalising pathology differed between surveys. The samples excluded people in aged-care institutions. ConclusionsWhile findings do not rule out that other measurement errors may be present (e.g., age-related bias in the remaining items), these results support the validity of the screening items in the CIDI and AUDADIS-IV. Low prevalence estimates of internalising disorders in older adults are unlikely attributable to differences in response patterns to screening items.

Divergent Effects of Aging and Sex on Vasoconstriction to Endothelin in Coronary Arterioles

The risk for cardiovascular disease increases with advancing age; however, the chronological development of heart disease differs in males and females. The purpose of this study was to determine whether age-induced alterations in responses of coronary arterioles to the endogenous vasoconstrictor, endothelin, are sex-specific. Coronary arterioles were isolated from young and old male and female rats to assess vasoconstrictor responses to endothelin (ET), and ETa and ETb receptor inhibitors were used to assess receptor-specific signaling. In intact arterioles from males, ET-induced vasoconstriction was reduced with age, whereas age increased vasoconstrictor responses to ET in intact arterioles from female rats. In intact arterioles from both sexes, blockade of either ETa or ETb eliminated age-related differences in responses to ET; however, denudation of arterioles from both sexes revealed age-related differences in ETa-mediated vasoconstriction. In arterioles from male rats, ETa receptor protein decreased, whereas ETb receptor protein increased with age. In coronary arterioles from females, neither ETa nor ETb receptor protein changed with age, suggesting age-related changes in ET signaling occur downstream of ET receptors. Thus, aging-induced alterations in responsiveness of the coronary resistance vasculature to endothelin are sex-specific, possibly contributing to sexual dimorphism in the risk of cardiovascular disease with advancing age.

Age-Related Differences in Response to High-Fat Feeding on Adipose Tissue and Metabolic Profile in ZDSD Rats

The recruitment of new fat cells through adipogenesis may prevent the development of obesity-related comorbidities. However, adipogenic capacity is markedly reduced in mature adults. This study examined how initiation of high-fat feeding at different phases of adulthood modified adipose tissue (AT) morphology and obesity phenotype in obese and diabetic Zucker Diabetic Sprague Dawley (ZDSD) rats. For this, rodents were provided high-fat diet (HFD) beginning at 63, 84, or 112 d after parturition until termination (n = 6). At termination, ZDSD rats fed HFD beginning at 63 d after parturition (early adulthood) exhibited greater body fat and lower lean mass without significant changes to energy intake or body weight. Moreover, early high fat feeding increased adipocyte size and number, whereas these effects were absent at 84 or 112 d after parturition. At 126 d after parturition, there were no detectable transcript differences in PPARγ or C/EBPα. However, rodents provided HFD in early adolescence exhibited lower expression of canonical Wnt signaling intermediates. Corresponding with these changes was a marked reduction in AT-specific inflammation, as well as overall improvement in systemic glucose, lipid, and inflammatory homeostasis. Taken together, these data indicate that dietary regulation of adipocyte recruitment in adolescence may represent a major determinant of obesity phenotype.

Diet‐induced obesity has a differential effect on adipose tissue and macrophage inflammatory responses of young and old mice

Obesity and aging are both associated with increased inflammation in adipose tissue. In this study, we investigated effect of diet-induced obesity on inflammatory status in young and old mice. Young (2 months) and old (19 months) C57BL/6 mice were fed a low-fat (10%, LF) or high-fat (60%, HF) diet for 4.5 months. Adipose tissue from old/LF mice expressed higher levels of IL-1β, IL-6, TNFα, and cyclooxygenase-2 mRNA compared with young/LF mice. HF diet upregulated expression of all these inflammatory markers in young mice to the levels seen in the aged. Adipocytes, but not stromal vascular cells, from old/LF mice produced more IL-6, TNFα, and prostaglandin (PG)E2 than those from young/LF mice. HF diet resulted in an increase of all these markers produced by adipocytes in young, but only TNFα in old mice. PGE2 produced by peritoneal macrophages (Mϕ's) was upregulated with aging, and HF diet induced more IL-6, TNFα, and PGE2 production in young but not in old mice. Thus, HF diet/obesity induces an inflammatory state in both visceral fat cells and peritoneal Mϕ's of young mice, but not so in old mice. Together, these results suggest that HF diet-induced obesity may speed up the aging process as characterized by inflammatory status. This study also indicates that animals have a differential response, depending on their ages, to HF diet-induced obesity and inflammation. This age-related difference in response to HF diet should be considered when using inflammation status as a marker in investigating adverse health impacts of HF diet and obesity.

Attentional bias and emotion in older adults: Age-related differences in responses to an emotional Stroop task

Attentional bias and emotion in older adults: Age-related differences in responses to an emotional Stroop task The purpose of the study was to examine whether older adults show an emotional interference effect in a Stroop task, and whether their RTs differ with regard to age, gender and tendencies of mood regulation (to improvement and/or deterioration). The sample consisted of 60 participants at the age from 65 to 85. Emotional version of Stroop task and the Mood Regulation Scales were used. The results showed no significant differences in RTs to emotional and neutral words. Unexpectedly, a speeding effect was observed with the age of women. It appeared also that the effect of mood regulation tendencies was not significant for RTs. The last two effects are not consistent with the literature on cognitive and emotional aging.

Age-Related Differences in Pulmonary and Cardiovascular Responses to SiO2 Nanoparticle Inhalation: Nanotoxicity Has Susceptible Population

Epidemiologic studies have revealed that pollution by ambient particulates is associated with respiratory and cardiovascular diseases, particularly in older people. Toxicologic sensitivity of nanoparticles in different ages was investigated for the first time to demonstrate and explain an age-related difference in response to manufactured nanoparticles. Young, adult, and old rats physiologically inhaled air containing aerosol of manufactured SiO2 nanoparticles (24.1 mg/m3; 40 min/day) for four weeks. Changes in serum biomarkers, hemorheologic, pulmonary inflammation, heart injury, and pathology in rats of different ages and their corresponding controls were compared. Inhalation of SiO2 nanoparticles under identical conditions caused pulmonary and cardiovascular alterations in old rats, yet less change in young and adult rats, including pulmonary inflammation, myocardial ischemic damage, atrio-ventricular blockage, and increase in fibrinogen concentration and blood viscosity. Old individuals were more sensitive to nanoparticle exposure than the young and adult rats. The risk of causing pulmonary damages was: old > young > adult The risk of cardiovascular disorder was observed only in old age. Our results suggest that different ages may require different biomarkers for identifying pulmonary toxicity during inhalation of nanoparticles.

The in vitro anticoagulant effects of Danaparoid, Fondaparinux, and Lepirudin in children compared to adults

Introduction Major physiological differences in the coagulation system of children compared to that of adults are well documented. We have previously investigated the age-related differences in response to Unfractionated Heparin (UFH). However, the impact of developmental haemostasis on more recent anticoagulant drugs is unknown. A number of these drugs are approved for use in specific indications in adults and none are approved for use in children. This study aimed to determine whether age-related differences in effect and impact on monitoring tests exist in vitro for danaparoid, fondaparinux and lepirudin. Materials and Methods Plasma samples were obtained from healthy children and pooled into age-specific pools, in order to obtain sufficient quantity of plasma required for the analysis of the three drugs. Each age-specific pool was spiked with different concentrations of danaparoid, fondaparinux and lepirudin and response was measured using standard techniques. All experiments were repeated using three separate plasma pools. The effect of each drug in children's plasma was compared to the effect in the respective adult plasma pool. Results Age-related differences in effect on thrombin potential and monitoring tests were observed only with the drug lepirudin. Specifically, APTT for children up to 5 years of age was increased compared to adults; all children had lower ECT results compared to adults; children up to 10 years of age had increased inhibition of ETP as compared to adults. Conclusions This study confirms age-related differences in response to anticoagulants with predominant anti-IIa effect and highlights the need for further research into this area.

Effects of Graded Doses of Testosterone on Erythropoiesis in Healthy Young and Older Men

Erythrocytosis is a dose-limiting adverse effect of testosterone therapy, especially in older men. Our objective was to compare the dose-related changes in hemoglobin and hematocrit in young and older men and determine whether age-related differences in erythropoietic response to testosterone can be explained by changes in erythropoietin and soluble transferrin receptor (sTfR) levels. We conducted a secondary analysis of data from a testosterone dose-response study in young and older men who received long-acting GnRH agonist monthly plus one of five weekly doses of testosterone enanthate (25, 50, 125, 300, or 600 mg im) for 20 wk. The study took place at a General Clinical Research Center. Participants included 60 older men aged 60-75 yr and 61 young men aged 19-35 yr. Outcome measures included hematocrit and hemoglobin and serum erythropoietin and sTfR levels. Hemoglobin and hematocrit increased significantly in a linear, dose-dependent fashion in both young and older men in response to graded doses of testosterone (P<0.0001). The increases in hemoglobin and hematocrit were significantly greater in older than young men. There was no significant difference in percent change from baseline in erythropoietin or sTfR levels across groups in either young or older men. Changes in erythropoietin or sTfR levels were not significantly correlated with changes in total or free testosterone levels. Testosterone has a dose-dependent stimulatory effect on erythropoiesis in men that is more pronounced in older men. The testosterone-induced rise in hemoglobin and hematocrit and age-related differences in response to testosterone therapy may be mediated by factors other than erythropoietin and sTfR.

Age-related differences in responses to thoughts of one's own death: mortality salience and judgments of moral transgressions.

Two experiments explored age differences in response to reminders of death. Terror management research has shown that death reminders lead to increased adherence to and defense of one's cultural worldview. In Study 1, the effect of mortality salience (MS) on evaluations of moral transgressions made by younger and older adults was compared. Whereas younger adults showed the typical pattern of harsher judgments in response to MS, older adults did not. Study 2 compared younger and older adults' responses to both the typical MS induction and a more subtle death reminder. Whereas younger adults responded to both MS inductions with harsher evaluations, older adults made significantly less harsh evaluations after the subtle MS induction. Explanations for this developmental shift in responses to reminders of death are discussed.

Age-related differences in responses to affective vs. rational ads for hedonic vs. utilitarian products

This research investigated the moderating role of product category type (hedonic vs. utilitarian) on age-related differences in responses to affective vs. rational ads. An experiment showed that elderly consumers (age 65 plus) had more favorable attitudes toward affective (vs. rational) ads, regardless of product category type. In contrast, young adult consumers (age 18–25) favored affective ads only for hedonic products. They favored rational ads for utilitarian products. Results of the experiment imply that, to explain age-related differences in decision making, researchers must take into account age-related differences in motivational states apart from apparent shortfalls in cognition.

Immediate early gene response to antidepressants acting on the noradrenergic system differs between juvenile and adult rats

Adults respond to antidepressant drugs acting on the noradrenergic (NE) system, .e.g., desipramine (DMI), and on the serotonin (5HT) system, SSRIs such as escitalopram (E). Children and adolescents generally respond only to SSRIs. We hypothesize this is due to the slower development of the NE system and that drugs acting on this system produce different effects in developing vs. adult brain. The immediate early genes (IEGs), Arc and zif268, play important roles in learning and memory and in brain regions associated with mood. Adult and juvenile (PND 9) rats received E, DMI or vehicle for 4 days and were sacrificed on day 5. Although both treatments altered IEG expression in some brain regions, E produced similar changes in adults and juveniles with few exceptions. By contrast, DMI produced differential changes in IEG expression in many regions. These studies demonstrate that juvenile and adult brains respond in a similar manner to drugs acting on the 5HT system, but very differently to drugs acting on the NE system. This is consistent with our hypothesis that different rates of development in neuronal systems lead to age-related differences in response to antidepressants. Supported by MH66959 (DBB).

Effect of azoxymethane and curcumin on transcriptional levels of cyclooxygenase-1 and -2 during initiation of colon carcinogenesis

Background. Curcumin is well documented as an effective colonic chemopreventive agent in preclinical studies. Inhibition of arachidonic acid metabolism has been considered one of anticarcinogenic mechanisms of curcumin. We recently reported resistance of middle-aged F344 male rats to inhibition of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) by curcumin (Nutr Cancer, 48, 37–43). It was important to confirm this finding and to find potential mechanisms responsible, as loss of preventive activity of curcumin due to aging was a novel finding, with important implications for human intervention trials. Methods. To confirm our previous findings, and investigate arachidonic acid metabolism as a potential mechanism of age-related differences in response to curcumin, middle-aged F344 male rats were given AOM injections after being fed their experimental diets, 0.6% curcumin or control diet. Colonic ACF were evaluated and colonic levels of cyclooxygenase (COX)-1 and 2 mRNA and prostaglandin E2 (PGE2) were measured. Next, we investigated the short-term effect of AOM and curcumin on arachidonic acid metabolism in young rats. Six week-old rats were given injections of either AOM or untreated following their experimental diets. Colonic COX-1 and COX-2 mRNA as well as PGE2 levels were measured shortly after AOM treatment. Lastly, three different ages of F344 rats were treated with either AOM or saline, and colonic COX-1 and COX-2 mRNA levels were measured shortly after the injections to find if aging alters the effect of AOM on COX mRNA expression. Results. In middle-aged rats, dietary curcumin did not reduce the number of ACF and surprisingly increased colonic levels of COX-2 mRNA. Colonic COX-2 and PGE2 levels were also significantly increased in young rats fed curcumin after AOM injections. Interestingly, AOM did not affect COX-2 but decreased COX-1 expression in all ages. Conclusions. Our study suggests that during initiation, AOM inhibits colonic COX-1 expression without affecting COX-2 and dietary curcumin may increase COX-2 expression to compensate AOM-induced reduction of COX-1 expression.

Age related differences in the immune response to vaccination and infection with Mycoplasma gallisepticum

Several studies have suggested that there are age related differences in the responses of chickens to vaccination and infection with Mycoplasma gallisepticum, but there have not been any systematic comparisons of the responses of young birds to vaccination with those of birds the same age to infection. The aim of the studies described here was to examine the immune responses of chickens between 1 and 6 weeks of age to vaccination and to infection with M. gallisepticum. Birds under 4 weeks of age developed significantly more severe clinical signs after infection with virulent M. gallisepticum than birds that were 4 or 6-weeks old at the time of infection, with greater concentrations of M. gallisepticum in the trachea. Chickens younger than 4 weeks old at the age of vaccination were protected from clinical signs of disease after challenge and from development of more severe lesions in the trachea and air sacs, although this protective immunity was significantly less effective in controlling the replication of M. gallisepticum in the trachea. Examination of the subsets of lymphocytes infiltrating the tracheal mucosa did not detect any age related differences. Thus the ts-11 vaccine has been shown to be safe in birds between 1 and 4 weeks of age and to be effective in preventing development of severe disease in them after challenge, even though birds of the same age were more susceptible to development of disease when infected with virulent M. gallisepticum.

Adenylate Cyclase-Mediated Forms of Neuronal Plasticity in Hippocampal Area CA1 Are Reduced With Aging

Beta-adrenergic receptors and the cyclic AMP signaling pathway play an important role in neuronal plasticity and in learning and memory and are known to change with aging. We examined the effects of beta-adrenergic stimulation paired with 5-Hz low frequency stimulation (LFS) of Schaffer collateral-commissural afferents on population spike amplitude in area CA1 of hippocampal slices from young (3 mo) and aged (22 mo) Fischer 344 rats. Application of the beta-adrenergic agonist isoproterenol (1 microM) for 10 min followed immediately by 3 min LFS produced long-lasting potentiation in young hippocampi, but the magnitude of potentiation in aged rats was significantly attenuated and was not long-lasting. In slices prepared from young rats, long-term potentiation (LTP) induced by this protocol occludes subsequent attempts to produce conventional high frequency stimulation-induced LTP, and vice versa, suggesting that these two forms of potentiation share one or more molecular mechanisms. Age-related differences in response to LFS alone were not observed, but significant differences in response to beta-adrenergic stimulation were apparent. Similarly, significant age-related differences in response to direct activation of adenylate cyclase with forskolin (10 microM) were observed. In both age groups, this enhancement produced by isoproterenol or forskolin is only transient, returning to baseline within 60 or 90 min, respectively. Taken together, these studies of adenylate cyclase-mediated forms of potentiation in area CA1 suggest that there is an age-related defect, either upstream or downstream of adenylate cyclase activation, in this important signaling system. Such changes may contribute to the compromised performance on memory tasks that is often observed with normal aging.

Adenylate Cyclase-Mediated Forms of Neuronal Plasticity in Hippocampal Area CA1 Are Reduced With Aging

Beta-adrenergic receptors and the cyclic AMP signaling pathway play an important role in neuronal plasticity and in learning and memory and are known to change with aging. We examined the effects of β-adrenergic stimulation paired with 5-Hz low frequency stimulation (LFS) of Schaffer collateral-commissural afferents on population spike amplitude in area CA1 of hippocampal slices from young (3 mo) and aged (22 mo) Fischer 344 rats. Application of the β-adrenergic agonist isoproterenol (1 μM) for 10 min followed immediately by 3 min LFS produced long-lasting potentiation in young hippocampi, but the magnitude of potentiation in aged rats was significantly attenuated and was not long-lasting. In slices prepared from young rats, long-term potentiation (LTP) induced by this protocol occludes subsequent attempts to produce conventional high frequency stimulation-induced LTP, and vice versa, suggesting that these two forms of potentiation share one or more molecular mechanisms. Age-related differences in response to LFS alone were not observed, but significant differences in response to β-adrenergic stimulation were apparent. Similarly, significant age-related differences in response to direct activation of adenylate cyclase with forskolin (10 μM) were observed. In both age groups, this enhancement produced by isoproterenol or forskolin is only transient, returning to baseline within 60 or 90 min, respectively. Taken together, these studies of adenylate cyclase-mediated forms of potentiation in area CA1 suggest that there is an age-related defect, either upstream or downstream of adenylate cyclase activation, in this important signaling system. Such changes may contribute to the compromised performance on memory tasks that is often observed with normal aging.