Caloric restriction (CR: reducing caloric intake 30-40 percent below ad libitum levels) remains the only intervention that reproducibly extends lifespan, reduces the incidence and delays the onset of age-related disease, enhances stress protection, and attenuates functional decline in mammals. Although the effects of CR on aging have been widely reported in rodents and other short-lived species, its application to a primate model is relatively new and still unproven. In 1987, the National Institute on Aging began the first well controlled long-term study in a species with a considerably longer lifespan and a closer physiology to humans. Monkeys benefit from CR with a lower body weight, body fat, and blood glucose and thus are at lower risk for developing diabetes. Changes in several endocrine measures indicate an altered hormonal axis. Despite the caloric deficit, female monkeys are not reproductively compromised and both males and females may benefit immunologically. ? We have developed a behavior program to test learning, memory, motor function, and activity. Tests of delayed responses taxing short-term memory are the best characterized in aging monkeys. Performance in tasks such as object discrimination and object reversal were age-sensitive but there was no significant difference between diet groups. The lack of diet effects in the object discrimination tasks is important for reducing concerns about diet effects on non-cognitive performance factors. More complex tasks using custom-made portable touch-screen panels are currently underway. Motor performance was assessed using an automated monkey Movement Assessment Panel (mMAP) that has reproducibly and reliably measured reaction time, coarse-motor, and fine-motor movement in rhesus monkeys and humans. In our study, an age-related decline in fine motor performance has been observed that was partially ameliorated in the CR monkeys. An-age related decline in striatum D2 dopamine receptors measured by PET analysis was also apparent which may be a factor for impaired motor performance. ? We continue to monitor morbidity and mortality but the number of deaths and diagnosed diseases remains too low for conclusive statistical analyses. ? ? ? In the last year we have started two new studies which are still in the early stages of data collection. ? 1. Assessment of a possible model of Alzheimers disease in rhesus and squirrel monkeys.? We will determine if a chemical lesion using the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2 bromobenzylamine (DSP-4), which produces selective noradrenergic deafferenation in the cortex and hippocampus.of the locus coeruleus, will accelerate the deposition of amyloid- and corresponding neuroinflammation.? ? 2) Resveratrols effect on diet induced obesity in rhesus macaques.? We will study the protective effect of resveratrol on apoptosis and insulin resistance in obese monkeys. This will identify if animals fed a resveratrol supplemented diet are as protected against deleterious damage as has been shown in rodents.
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