title: Reduction of low grade inflammation restores blunting of postprandial muscle anabolism and limits sarcopenia in old rats.
abstract: Ageing is characterized by a decline in muscle mass that could be explained by a defect in the regulation of postprandial muscle protein metabolism. Indeed, the stimulatory effect of food intake on protein synthesis and its inhibitory effect on proteolysis is blunted in old muscles from both animals and humans. Recently, low grade inflammation has been suspected to be one of the factors responsible for the decreased sensitivity of muscle protein metabolism to food intake. This study was undertaken to examine the effect of long-term prevention of low grade inflammation on muscle protein metabolism during ageing. Old rats (20 months of age) were separated into two groups: a control group and a group (IBU) in which low grade inflammation had been reduced with a non-steroidal anti inflammatory drug (ibuprofen). After 5 months of treatment, inflammatory markers and cytokine levels were significantly improved in treated old rats when compared with the controls: -22.3% fibrinogen, -54.2% alpha2-macroglobulin, +12.6% albumin, -59.6% IL(6) and -45.9% IL(1beta) levels. As expected, food intake had no effect on muscle protein synthesis or muscle proteolysis in controls whereas it significantly increased muscle protein synthesis by 24.8% and significantly decreased proteolysis in IBU rats. The restoration of muscle protein anabolism at the postprandial state by controlling the development of low grade inflammation in old rats significantly decreased muscle mass loss between 20 and 25 months of age. In conclusion, the observations made in this study have identified low grade inflammation as an important target for pharmacological, nutritional and lifestyle interventions that aim to limit sarcopenia and muscle weakness in the rapidly growing elderly population in Europe and North America.
authors.affiliation: Inra, UMR 1019 Nutrition Humaine, Saint Genés Champanelle, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rieu
authors.forename: Hugues
authors.initials: H
authors.lastname: Magne
authors.forename: Isabelle
authors.initials: I
authors.lastname: Savary-Auzeloux
authors.forename: Julien
authors.initials: J
authors.lastname: Averous
authors.forename: Cécile
authors.initials: C
authors.lastname: Bos
authors.forename: M A
authors.initials: MA
authors.lastname: Peyron
authors.forename: Lydie
authors.initials: L
authors.lastname: Combaret
authors.forename: Dominique
authors.initials: D
authors.lastname: Dardevet
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D004435:Eating / Q000187:drug effects / Q000502:physiology; D007052:Ibuprofen / Q000008:administration & dosage; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008660:Metabolism / Q000187:drug effects / Q000502:physiology; D009124:Muscle Proteins / Q000096:biosynthesis / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D019518:Postprandial Period / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D055948:Sarcopenia / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009124:Muscle Proteins; D007052:Ibuprofen