The proposed research seeks to extend the dietary restriction paradigm of retarded aging to a marsupial mammal--the Virginia Opossum (Didelphis virginiana)--which is distantly related to both laboratory rodents and humans. The extent to which the paradigm is verified in the opossum will be directly relevant to the probability that retarded aging via dietary restriction is a general mammalian trait as opposed to a physiological quirk of murine rodents. Actuarial aging will be measured in two laboratory populations--a fully-fed (FF) control group and a dietary- restricted group (DR) that is given an isonutrient diet which contains 70% of the calories of the FF diet. In addition to actuarial data, relative aging in the two groups will be assessed by serial monitoring of: (a) the temporal pattern of reproductive cycling, (b) denaturation time of tail tendon collagen, (c) glycation of hemoglobin and blood serum protein, collagen from skin and tendon, (plus postmortem analyses of aorta collagen and eye lens proteins), and (d) a behavioral strength and agility test. All of these parameters are known or suspected to be general biomarkers of aging. In addition, a major goal of the proposal will be the longitudinal monitoring of serum osteocalcin (a potential early diagnostic parameter bone pathology), because elderly opossums show postural and gross morphological changes suggesting extensive bone loss. Also, in order to assess whether DR is affecting longevity through a reduction of metabolic rate, three-day metabolic expenditures of all experimental groups will be assayed using doubly-labelled water. Age-related general pathology will be assessed by diagnostic blood (hematology and blood chemistry) and urine analyses, and cause of death determined by standard gross-and histopathology. A thorough characterization of the opossum's age-related pathology should also reveal the extent to which it might be a useful model of specific pathologies.