Introduction: Glutamine is the most abundant free amino acid in the body and has its primary source in skeletal muscle, from where it is released into the bloodstream and transported to a variety of tissues such the gut. The size of the muscle glutamine pool may be related to lean body mass and so, to sarcopenia Objectives: Because glutamine is known to have a specific role in very old rats (up to 25 months of age), the aim of this study is to demonstrate that glutamine is the cornerstone of sarcopenia with advanced age. For this reason, we have orally supplemented female rats (27 months) with glutamine (20% of diet protein) intermittently, before animals became very old (named long-term treatment with glutamine). Rats were studied after the last glutamine cure Material and methods: Skeletal muscle (tibialis anterior) and gut were dissected and weighed. A 2-cm length of the proximal part of the jejunum was removed for measurements of intestinal histomorphometry Results: Muscle mass decreased by ~ 20 % with advanced age. No difference was observed in skeletal muscle mass with glutamine supplementation. However, glutamine synthesis was enhanced in skeletal muscle from very old female rat as previously reported. Glutamine played a role in maintaining mass of splanchnic tissues. Total intestine mass was significantly higher in glutamine supplemented very old rats than in controls (~15%). By histomorphometry, we demonstrated that villus height increased with glutamine supplementation in very old female rats; this increase was similar to that measured in gut mass Discussion: Long-term treatment with glutamine had positive effects on very old rats: 1) it prevented the loss of body weight, but, 2) it did not prevent the inevitable sarcopenia because of its inefficiency to limit the loss of muscle mass due to aging and, 3) it maintained or improved the gut mass. Long-term treatment with glutamine essentially played a role in maintaining intestine integrity and intestinal immune function. Indeed, villus height was improved by this treatment Consequently, the observed increase in glutamine requirements can be explained by the increased use of glutamine by the gut. Glutamine may play a role in repairing possible gut mucosal deterioration due to aging by increasing mucosal protein synthesis and decreasing ubiquitin-dependent proteolysis, as previously reported in healthy humans. Conclusion: Glutamine is not the cornerstone of sarcopenia in very old individuals even if a very high synthesis capacity is maintained in aging atrophied-muscle