Background & aims: Muscle is an important site of Gln synthesis and release in the whole body, while liver can take up circulating Gln even if it has the capacity to both degrade and synthesize Gln. During fasting, skeletal muscle in rats exports large amounts of Gln but also increases Gln production by glutamine synthetase (GS) to maintain its Gln pool, whatever the age. The aim of this study was to determine whether fasting induced GS activity in muscle may have conse- quences on liver Gln homeostasis during aging (by changing GS and glutaminase (GA) activities). Methods: Liver GS and GA activities were assessed in fed and 5 day fasted male Wistar rats during aging (2, 5, 15, 22 and 24 months). To compare potential cooperation between liver and muscle, GS activity was also measured in skeletal muscle. Results: After 5 days fasting, both total GS and GA activities in liver were decreased irrespective of age. As expected, muscle GS activity was increased by a factor of 1.5-2 in 2 to 24 month rats. In addition, 24 month fed and fasted rats had the same GS response. In contrast, in the fed state, both age and nutritional state played a role in the response of GA activity. Conclusion: Five day fasting induced an adaptation of Gln metabolism in male Wistar rats, in relation to aging. Muscle and liver synergistically played a role in this regulation. The specific role of Gln in satisfying increased requirements in very old rats was confirmed.