Psychomotor Tasks Research Articles

Effect of chronic caffeine intake on choice reaction time, mood, and visual vigilance

The stimulatory effects of acute caffeine intake on choice reaction time, mood state, and visual vigilance are well established. Little research exists, however, on the effects of chronic caffeine ingestion on psychomotor tasks. Therefore, the purpose of this study was to evaluate the effects of 5 days of controlled caffeine intake on cognitive and psychomotor performance. Three groups of 20 healthy males (age = 22 ± 3 years, mass = 75.4 ± 7.9 kg, body fat percentage = 11.2 ± 5.1%) twice completed a battery of cognitive and psychomotor tasks: after 6 days of 3 mg·kg − 1 day − 1 caffeine equilibration (Day 6), and after 5 days of experimental (0 [G0], 3 [G3], or 6 [G6] mg·kg − 1 day − 1 ) caffeine intake (Day 11). Groups were randomized and stratified for age, mass, and body composition; all procedures were double-blind. Cognitive analyses involved a visual four-choice reaction time test, a mood state questionnaire, and a visual vigilance task. Experimental chronic caffeine intake did not significantly alter the number of correct responses or the mean latency of response for either the four-choice reaction time or the visual vigilance tasks. The Vigor–Activity subset of the mood state questionnaire was significantly greater in G3 than G0 or G6 on Day 11. All other mood constructs were unaffected by caffeine intake. In conclusion, few cognitive and psychomotor differences existed after 5 days of controlled caffeine ingestion between subjects consuming 0, 3, or 6 mg·kg − 1 day − 1 of caffeine, suggesting that chronic caffeine intake (1) has few perceptible effects on cognitive and psychomotor well-being and (2) may lead to a tolerance to some aspects of caffeine's acute effects.

Effect of incremental exercise on initiation and movement times in a choice response, whole body psychomotor task

Objectives: To examine how exercise at moderate and maximal intensities affects performance on a choice response time, whole body psychomotor task. Methods: Subjects (n = 12) were tested on a...

Combined effects of methamphetamine and zolpidem on performance and mood during simulated night shift work

Individuals who work irregular or rotating shifts often use stimulants and sedatives to offset shift-change-related mood and performance decrements. During this simulated shift work study the acute effects of the stimulant, methamphetamine were examined, and the effects of the hypnotic, zolpidem, and the combination were assessed during the shift after drug administration. Eight volunteers completed this 21-day, within-participant, residential laboratory study during which they received a single oral methamphetamine dose (0 or 10 mg) 1 h after waking, i.e., before task performance, and a single oral zolpidem dose (0 or 10 mg) 1 h before bedtime under 2 shift conditions: day shift and night shift. When participants received placebo at both dosing times, performance on some psychomotor tasks (e.g., the digit-symbol substitution task) and on some measures of mood (e.g., ratings of “Energetic”) were disrupted during the night shift, relative to the day shift. Methamphetamine alone eliminated virtually all shift-related disruptions, while zolpidem alone and the drug combination produced few effects. These data indicate that shift changes produce performance impairments and mood alterations that are improved by a single low to moderate dose of methamphetamine. Zolpidem, given alone or in combination with methamphetamine, did not alleviate most shift-change mood and performance effects.

Dietary Caffeine, Performance and Mood: Enhancing and Restorative Effects after Controlling for Withdrawal Reversal

This study aimed to determine whether sustained (i.e. dietary) use of caffeine has net effects on performance and mood compared with sustained abstinence, and whether dietary caffeine restores performance and mood adversely affected by sleep restriction. Participants (n = 96) alternated weekly between ingesting placebo and caffeine (1.75 mg/kg) three times daily for 4 consecutive weeks, while either rested or sleep restricted. Performance involved either a single task requiring sustained vigilance or a varied battery of brief psychomotor and cognitive tasks, and mood was assessed using the Profile of Mood States. Caffeine had no significant net enhancing effects for either performance or mood when participants were rested, and produced no net restorative effects when performance and mood were degraded by sleep restriction.

IMPACT OF EDUCATIONAL INTERVENTION ON CONFIDENCE AND COMPETENCE IN THE PERFORMANCE OF A SIMPLE SURGICAL TASK

Background: Many complex new procedures involve a learning curve, and patients treated by individuals who are new to a procedure may have more complications than those treated by a practitioner who has performed the intervention more frequently. Still, at some point on the learning curve, each individual must decide that he or she is qualified to perform a procedure, presumably on the basis of his or her level of confidence, background, education, and skill. To evaluate the interrelationship of these factors, we designed a study in which we assessed the performance of a simulated knee joint injection. Methods: Ninety-three practitioners attending a continuing medical education session on knee injection were randomized to receive skills instruction through the use of a printed manual, a video, or hands-on instruction; each performed one injection before and after instruction. The participants completed pre-instruction and post-instruction questionnaires gauging confidence and also provided self-assessments of their performances of injections before and after instruction. Self-assessments were compared with objective performance standards measured by custom-designed knee models with electronic sensors that detected correct needle placement. Results: Before instruction, the participants' confidence was significantly but inversely related to competent performance (r = –0.253, p = 0.02); that is, greater confidence correlated with poorer performance. Both men and physician-practitioners displayed higher pre-instruction confidence (p < 0.01), which was not correlated with better performance. After instruction, performance improved significantly in all three training groups (p < 0.001), with no significant differences in efficacy detected among the three groups (p = 0.99). After instruction, confidence correlated with objective competence in all groups (r = 0.24, p = 0.04); however, this correlation was weaker than the correlation between the participants' confidence and their self-assessment of performance (r = 0.72, p = 0.001). Conclusions: Even low-intensity forms of instruction improve individuals' confidence, competence, and self-assessment of their skill in performing the fairly straightforward psychomotor task of simulated knee injection. However, men and physicians disproportionately overestimated their skills both before and after training, a finding that worsened as confidence increased. The inverse relationship between confidence and competence that we observed before the educational intervention as well as the demographic differences that we noted should raise questions about how complex new procedures should be introduced and when self-trained practitioners should begin to perform them. Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

Impact of Educational Intervention on Confidence and Competence in the Performance of a Simple Surgical Task

Many complex new procedures involve a learning curve, and patients treated by individuals who are new to a procedure may have more complications than those treated by a practitioner who has performed the intervention more frequently. Still, at some point on the learning curve, each individual must decide that he or she is qualified to perform a procedure, presumably on the basis of his or her level of confidence, background, education, and skill. To evaluate the interrelationship of these factors, we designed a study in which we assessed the performance of a simulated knee joint injection. Ninety-three practitioners attending a continuing medical education session on knee injection were randomized to receive skills instruction through the use of a printed manual, a video, or hands-on instruction; each performed one injection before and after instruction. The participants completed pre-instruction and post-instruction questionnaires gauging confidence and also provided self-assessments of their performances of injections before and after instruction. Self-assessments were compared with objective performance standards measured by custom-designed knee models with electronic sensors that detected correct needle placement. Before instruction, the participants' confidence was significantly but inversely related to competent performance (r = -0.253, p = 0.02); that is, greater confidence correlated with poorer performance. Both men and physician-practitioners displayed higher pre-instruction confidence (p < 0.01), which was not correlated with better performance. After instruction, performance improved significantly in all three training groups (p < 0.001), with no significant differences in efficacy detected among the three groups (p = 0.99). After instruction, confidence correlated with objective competence in all groups (r = 0.24, p = 0.04); however, this correlation was weaker than the correlation between the participants' confidence and their self-assessment of performance (r = 0.72, p = 0.001). Even low-intensity forms of instruction improve individuals' confidence, competence, and self-assessment of their skill in performing the fairly straightforward psychomotor task of simulated knee injection. However, men and physicians disproportionately overestimated their skills both before and after training, a finding that worsened as confidence increased. The inverse relationship between confidence and competence that we observed before the educational intervention as well as the demographic differences that we noted should raise questions about how complex new procedures should be introduced and when self-trained practitioners should begin to perform them.

Smoked cocaine discrimination in humans: Effects of gabapentin

γ-Aminobutyric acid (GABA) agonists, such as the GABA analogue, gabapentin, may provide new avenues for pharmacological treatment of cocaine dependence. The purpose of this study was to develop a smoked cocaine drug discrimination procedure in humans to test the effects of gabapentin maintenance on the discriminative stimulus, subjective, cognitive and cardiovascular effects of smoked cocaine. Eight male, nontreatment-seeking, cocaine-dependent volunteers, residing on an inpatient research unit for 47 days completed a within-subjects, counter-balanced design. Participants learned to discriminate between cocaine (25 mg) and placebo, and once the criterion for discrimination was met, smoked cocaine dose-effect functions (0, 6, 12, 25 and 50 mg) were determined under three gabapentin maintenance conditions (0, 600 and 1200 mg/day po). The highest dose of gabapentin tested (1200 mg/day) decreased the discriminative stimulus effects of cocaine (6 mg), decreased cocaine craving by 41–53% following cocaine administration (6 and 12 mg), and increased heart rate following either placebo or cocaine (12 mg) administration. Gabapentin did not significantly affect psychomotor task performance or the subjective effects of cocaine. Although the direction of gabapentin's effects was appropriate for a potential treatment medication, i.e., a decrease in cocaine-elicited craving and a decrease in cocaine's discriminative stimulus effects, these effects were limited to low doses of cocaine. The results suggest gabapentin may not produce effects sufficiently robust to be clinically useful, at least at this dose regimen.

Compensating for alcohol-induced impairment of control: effects on inhibition and activation of behavior

Studies have shown that expectations of alcohol-induced impairment can produce adaptive responses to alcohol that reduce the degree of behavioral impairment displayed. However, compensatory effects have been variable for cognitive and psychomotor tasks. Using a model-driven approach to understanding behavioral control, the present study examined compensatory and impairment effects following the expectation and actual administration of alcohol on the ability to inhibit and activate behavior. Social drinkers (N=17) performed a cued go/no-go task that required quick responses to go targets and inhibition of responses to no-go targets under four conditions: no treatment, alcohol expectancy (placebo), 0.45 g/kg alcohol, and 0.65 g/kg alcohol. Inhibitory and activational aspects of behavioral control were impaired by both active doses of alcohol. Alcohol slowed response activation and increased failures to inhibit responses in a dose-dependent manner. Subjects also displayed a small, but statistically significant, compensatory improvement in inhibitory control in response to the expectation of alcohol. Moreover, individual differences in the compensatory response were related to differences in alcohol impairment. Those who displayed greater compensatory responses to placebo displayed the least impairment in response to alcohol. By modeling behavioral control as the net effect of countervailing activational and inhibitory influences, the study suggests that fundamental mechanisms of control might not display uniform compensatory reactions to alcohol-related cues. Greater consideration of how alcohol-related expectancies shape behaviors under the drug should lead to a better understanding of individual differences with respect to risk for alcohol abuse.

Cannabis and driving: the use of LC–MS to detect Δ 9-tetrahydrocannabinol (Δ 9-THC) in oral fluid samples

Cannabis is the most widely used illicit drug in the world. There is strong evidence from performance studies that Δ 9-THC has significant effects on the cognitive and psychomotor tasks associated with driving. New, easy and sensitive methods to detect impaired drivers are needed. Therefore, it is necessary the use of alternative biological samples which may be accurate, precise and with trustfully interpretation results. This article presents an LC–MS methodology for detecting Δ 9-tetrahydrocannabinol (Δ 9-THC) in oral fluid samples. The mean recovery was 79%, coefficients of variations were between 2.9% and 6.9% and the limits of detection (LOD) and quantitation (LOQ) were 1.0 ng/ml and 2.0 ng/ml, respectively. The method is sensitive, accurate and reproducible and may be utilized in ongoing controlled cannabinoid administration studies and in roadside studies and thus, important for the fields of forensic toxicology.

Metacognitive Processes Underlying Psychomotor Performance in Children with Differing Psychomotor Abilities

The use of metacognition differs with different levels of cognitive ability, but it is not known whether children of different psychomotor abilities use metacognition differently. This study used a think-aloud protocol to compare the active use of metacognition in children with different psychomotor abilities—high skill, average, developmental coordination disorder (DCD)—during a ball-throwing task. Children with DCD did not verbalize fewer or different metacognitive concepts than either the average or high skill children; however, relative to their counterparts, a significant median proportion of the concepts verbalized by children with DCD were found to be inappropriate or inaccurate. These findings reflect ineffective metacognitive processing by children with DCD during a psychomotor task.

P3-375 Correlation between patterns of atrophy and psychomotor task performance in early huntington's disease

P3-375 Correlation between patterns of atrophy and psychomotor task performance in early huntington's disease

The Effect of Repeated Isoflurane Anesthesia on Spatial and Psychomotor Performance in Young and Aged Mice

Exposure to general anesthesia may contribute to postoperative cognitive impairment in elderly patients, but the relationship remains poorly understood. We investigated whether aged mice, 18-19 mo, are more susceptible to postanesthetic cognitive impairment than young mice, 3-4 mo, using spatial memory (Barnes maze) and psychomotor (rotarod) tasks. Initially we studied the effect of a single anesthetic episode on asymptotic maze performance. We then tested whether repeated anesthesia would impair spatial memory and psychomotor performance to a greater extent in aged mice. Mice were anesthetized with isoflurane (1.4% atm) for 30 min; controls received 90% oxygen. Anesthesia, administered during the asymptotic period of maze learning, did not impair performance tested the following day (P > 0.05). Repeated anesthesia, 2-3 h after each session, did not impair overall maze or rotarod performance in young or aged mice (P > 0.05). Spatial learning appeared to be facilitated by anesthesia, F(1,204) = 7.97, P < 0.01 for pooled results. Asymptotic performance-when learning had stabilized-remained unimpaired in both the maze and rotarod tasks. These results suggest that an age-related risk of anesthetic-induced impairment appears to be limited to acquisition of a novel motor skill and that anesthesia alone does not lead to prolonged cognitive impairments in aged mice. This study demonstrates that repeated isoflurane general anesthesia impaired psychomotor performance in aged mice during the initial learning period; however, spatial learning improved and, overall, spatial memory and psychomotor performance were unimpaired. Thus, general anesthesia alone does not appear to result in prolonged cognitive deficits in aged mice.

Probing opioid effects in major depression hydromorphone (HM) challenge

The opioid system may play a role in some symptoms of major depressive disorder (MDD). We hypothesized that depressed individuals would exhibit an altered response to the agonist HM compared to controls due to an altered function of opioid pathways. In a double-blind, placebo-controlled, randomized study, the effects of HM (6mg, oral) were measured before and 30, 60, 90, 120, 180 and 240 min. after HM intake. Patients with MDD (N=39; HM: 17; placebo: 22) were compared to controls (N=22; HM: 9; placebo: 13) using well-validated scales (e.g. Addiction Research Center Inventory), and psychomotor tasks (e.g. Tracking Test). HM produced time-dependent changes in subjective effects (e.g. VAS-Liking, ARCI-PCAG). Severely depressed (HAMD>24) subjects receiving HM showed significant improvement on negative symptoms compared to controls: differences in the ARCI negative effects composite scale in both peak - baseline and baseline-corrected area-under-the-curve (AUC) mean scores of subjective HM effects were significantly reduced in severely depressed vs. controls (peak - baseline: 96.5 vs. 201.1, p=0.05; AUC: 128.8 vs. 358.2, respectively, p=0.05). Tracking Test mean baseline-corrected % time over the road AUC scores were 10.4 for the severely depressed vs. −13.4 for moderately depressed (p<0.05) and vs. −0.02 for controls (NS). These findings suggest involvement of opioids in the neurobiology of depression. Clinical Pharmacology & Therapeutics (2004) 75, P3–P3; doi: 10.1016/j.clpt.2003.11.009

Objective psychomotor skills assessment of experienced and novice flexible endoscopists with a virtual reality simulator.

The objective of this study was to determine whether the GI Mentor II virtual reality simulator can distinguish the psychomotor skills of intermediately experienced endoscopists from those of novices, and do so with a high level of consistency and reliability. A total of five intermediate and nine novice endoscopists were evaluated using the EndoBubble abstract psychomotor task. Each subject performed three repetitions of the task. Performance and error data were recorded for each trial. The intermediate group performed better than the novice group in each trial. The differences were significant in trial 1 for balloons popped (P=.001), completion time (P=.04), and errors (P=.03). Trial 2 showed significance only for balloons popped (P=.002). Trial 3 showed significance for balloons popped (P=.004) and errors (P=.008). The novice group showed significant improvement between trials 1 and 3 (P<0.05). No improvement was noted in the intermediate group. Measures of consistency and reliability were greater than 0.8 in both groups with the exception of novice completion time where test-retest reliability was 0.74. The GI Mentor II simulator can distinguish between novice and intermediate endoscopists. The simulator assesses skills with levels of consistency and reliability required for high-stakes assessment.

Marijuana Withdrawal in Humans: Effects of Oral THC or Divalproex

Abstinence following daily marijuana use can produce a withdrawal syndrome characterized by negative mood (eg irritability, anxiety, misery), muscle pain, chills, and decreased food intake. Two placebo-controlled, within-subject studies investigated the effects of a cannabinoid agonist, delta-9-tetrahydrocannabinol (THC: Study 1), and a mood stabilizer, divalproex (Study 2), on symptoms of marijuana withdrawal. Participants (n=7/study), who were not seeking treatment for their marijuana use, reported smoking 6-10 marijuana cigarettes/day, 6-7 days/week. Study 1 was a 15-day in-patient, 5-day outpatient, 15-day in-patient design. During the in-patient phases, participants took oral THC capsules (0, 10 mg) five times/day, 1 h prior to smoking marijuana (0.00, 3.04% THC). Active and placebo marijuana were smoked on in-patient days 1-8, while only placebo marijuana was smoked on days 9-14, that is, marijuana abstinence. Placebo THC was administered each day, except during one of the abstinence phases (days 9-14), when active THC was given. Mood, psychomotor task performance, food intake, and sleep were measured. Oral THC administered during marijuana abstinence decreased ratings of 'anxious', 'miserable', 'trouble sleeping', 'chills', and marijuana craving, and reversed large decreases in food intake as compared to placebo, while producing no intoxication. Study 2 was a 58-day, outpatient/in-patient design. Participants were maintained on each divalproex dose (0, 1500 mg/day) for 29 days each. Each maintenance condition began with a 14-day outpatient phase for medication induction or clearance and continued with a 15-day in-patient phase. Divalproex decreased marijuana craving during abstinence, yet increased ratings of 'anxious', 'irritable', 'bad effect', and 'tired.' Divalproex worsened performance on psychomotor tasks, and increased food intake regardless of marijuana condition. Thus, oral THC decreased marijuana craving and withdrawal symptoms at a dose that was subjectively indistinguishable from placebo. Divalproex worsened mood and cognitive performance during marijuana abstinence. These data suggest that oral THC, but not divalproex, may be useful in the treatment of marijuana dependence.

The Effects of Leadership Style and Workload on Team Alarm Reaction Performance and Team Satisfaction

Previous research has indicated that flight crew communication problems cause the majority of human errors in aircraft cockpits. Such problems may further degrade reaction decisions to unreliable alarm signals. In this research we examine how leadership style and workload affect collective reactions to unreliable alarms. Seventeen psychology student dyads from Old Dominion University were randomly assigned to act as pilots or copilots while performing complex psychomotor and alarm response tasks. Dyad leaders (pilots) were assigned to exhibit autocratic or participative leadership behaviors. Dyads reacted to ten alarms in each condition and were randomly assigned to a low or high psychomotor task workload group. Results indicated that dyads in the low workload group reacted to alarms significantly faster than dyads in the high workload group. Also, copilots indicated higher leadership satisfaction in the participative style. These findings suggest that alarm designers consider workload when implementing alarm systems, and that pilots should be trained to exhibit participative leadership qualities.

Neuropsychological effects of long-term opioid use in chronic pain patients

Opioids are thought to worsen the performance of psychomotor tasks due to their sedating and mental-clouding effects. As a result, some safety regulations currently restrict the use of opioids when driving or using heavy equipment. We investigated the psychomotor effects of long-term opioid use in 144 patients with low back pain. All subjects were administered two neuropsychological tests (Digit Symbol and Trail Making Test-B) before being prescribed opioids for pain; tests were re-administered at 90- and 180-day intervals. Test scores significantly improved while subjects were taking opioids for pain, which suggests that long-term use of oxycodone with acetaminophen or transdermal fentanyl does not significantly impair cognitive ability or psychomotor function.

Dynamic Spatial Ability and Psychomotor Performance

Dynamic spatial ability is one's ability to estimate when a moving object will reach a destination, or one's skill in making time-to-contact (TTC) judgments. In 2 studies, we investigated the nature of dynamic spatial ability and its role in psychomotor (PM) task performance. In the first study, 405 basic military trainees were given both spatial and nonspatial versions of TTC and comparative arrival-time tasks, and we found that the spatial and nonspatial versions of the tasks were more highly correlated than the spatial tasks were to each other, suggesting that a timing, rather than a spatial, mechanism underlies performance of dynamic spatial tasks. In the second study with 376 military trainees, we found that performance on a set of PM tasks was predicted by a general working-memory (WM) Capacity factor (r = .45) and an orthogonal Temporal Processing (TP) factor (r = .55), suggesting the importance of the dynamic spatial, or of the TP factor, in many real-world activities.

Driving simulators in clinical practice.

Operating a motor vehicle is a complex psychomotor task that requires sustained vigilance. When sleepy, subjects have difficulty maintaining vigilance. As a result, inattention increases the risk of a motor vehicle collision. There is extensive literature that demonstrates that sleepy patients have poor performance and increased motor vehicle crashes. Determining an individual's risk of crash has not been possible solely on clinical grounds and as a result, a number of driving simulators have been developed/employed to aid in this process. While the data shows a consistent effect of sleepiness on driving and simulated driving performance, the role of these simulators in day to day clinical practice is still evolving.

How does calorie restriction work?

For almost 70 years, calorie restriction has been known to extend life span. Despite the extensive physiological characterization of this dietary regimen, the molecular basis for the slowing in aging remains unsolved. Recent findings have pinpointed a few molecular pathways that appear to regulate the aging process. In this review, we propose a molecular model for how calorie restriction works that incorporates these recent findings. Calorie restriction (CR) refers to a dietary regimen low in calories without undernutrition. It was first noted in the 1930s that food restriction significantly extends the life span of rodents (McCay et al. 1935). This longevity results from the limitation of total calories derived from carbohydrates, fats, or proteins to a level 25%–60% below that of control animals fed ad libitum (Richardson 1985; Weindruch et al. 1986). The extension in life span can approach 50% in rodents (Sohal and Weindruch 1996). CR extends life span in a remarkable range of organisms, including yeast, rotifers, spiders, worms, fish, mice, and rats (Weindruch and Walford 1988). Emerging data show that its effect may also apply to nonhuman primates (Lane et al. 2001). CR delays a wide spectrum of diseases in different experimental animals; for example, kidney disease, a variety of neoplasias, autoimmune disease, and diabetes (Fernandes et al. 1976; Sarkar et al. 1982; Fernandes and Good 1984; Kubo et al. 1984; Engelman et al. 1990; Shields et al. 1991; Johnson et al. 1997). CR reduces ageassociated neuronal loss in most mouse models of neurodegenerative disorders such as Parkinson’s disease (Duan and Mattson 1999) or Alzheimer’s disease (Zhu et al. 1999). However, beneficial effects in a mouse model for amyotrophic lateral sclerosis were not observed (Pedersen and Mattson 1999). The CR regimen also prevents age-associated declines in psychomotor and spatial memory tasks (Ingram et al. 1987) and loss of dendritic spines necessary for learning (Moroi-Fetters et al. 1989) and improves the brain’s plasticity and ability for selfrepair (Mattson 2000). Why does CR exert these effects? Because CR delays reproduction and promotes survival in times of scarcity, it may have been evolutionarily adaptive during boom/ bust cycles (Harrison 1989; Holliday 1989). Despite the plausibility of this reasoning, several challenges to the significance of CR studies in the laboratory have been made. Perhaps the restricted animals live longer simply because controls are overfed to the point of ill health. However, regimens in which animals are fed controlled amounts of food rather than ad libitum still show beneficial effects of low calories (Weindruch and Walford 1988). Another objection is that inbred strains of rodents are not representative of animals in the wild. For example, lab strains are selected for rapid reproduction and large litters (Miller et al. 1999). It has been argued that these animals may accordingly have shorter life spans than wild strains. By this reasoning, CR may simply correct a defect that has been created by domestication. However, the generality of CR in many different organisms, as mentioned above, supports the argument against this criticism. Even though benefits of CR have been known for many years, the mechanism(s) of its action remains unclear. Its complexity lies in multiple effects including metabolic, neuroendocrine, and apoptotic changes, which vary in intensity and exhibit striking differences among specific organ systems. Several major models to explain CR exist, but none satisfactorily integrates all of CR’s effects. In this review, we address the question of how CR might function to extend life span. We begin with a summary of several aging theories and classical views about the action of CR. Then we discuss how CR extends the life span in Saccharomyces cerevisiae. We extrapolate these findings from yeast to mammals and consider metabolic, neuroendocrine, and apoptotic shifts that may trigger longevity in the higher organisms. We conclude with a model of CR that integrates its effects on mammals.