We have determined that with 20 days of calorie restriction (CR; consuming 60% of ad libitum, food intake), animals (rats or mice) have increased insulin-stimulated glucose transport (i.e., glucose entry into cells) in skeletal muscle with increased activation of insulin signaling proteins playing an key role. We are initiating new studies that will focus on understanding the mechanisms that account for improved insulin sensitivity with long-term CR (several months to several years) in adult and old animals.