title: Aging related ER stress is not responsible for anabolic resistance in mouse skeletal muscle.
abstract: Anabolic resistance reflects the inability of skeletal muscle to maintain protein mass by appropriate stimulation of protein synthesis. We hypothesized that endoplasmic reticulum (ER) stress contributes to anabolic resistance in skeletal muscle with aging. Muscles were isolated from adult (8 mo) and old (26 mo) mice and weighed. ER stress markers in each muscle were quantified, and the anabolic response to leucine was assessed by measuring the phosphorylation state of S6K1 in soleus and EDL using an ex vivo muscle model. Aging reduced the muscle-to-body weight ratio in soleus, gastrocnemius, and plantaris, but not in EDL and tibialis anterior. Compared to adult mice, the expression of ER stress markers BiP and IRE1α was higher in EDL, and phospho-eIF2α was higher in soleus and EDL of old mice. S6K1 response to leucine was impaired in soleus, but not in EDL, suggesting that anabolic resistance contributes to soleus weight loss in old mice. Pre-incubation with ER stress inducer tunicamycin before leucine stimulation increased S6K1 phosphorylation beyond the level reached by leucine alone. Since tunicamycin did not impair leucine-induced S6K1 response, and based on the different ER stress marker regulation patterns, ER stress is probably not involved in anabolic resistance in skeletal muscle with aging.
authors.affiliation: Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Tervuursevest 101, Box 1500, 3001, Leuven, Belgium.
authors.forename: Sreeda
authors.initials: S
authors.lastname: Chalil
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Place Pierre de Coubertin 1, 1348, Louvain-la-Neuve, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pierre
authors.affiliation: Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Gustav Mahlerlaan 3004, 1081 LA, Amsterdam, The Netherlands.
authors.forename: Astrid D
authors.initials: AD
authors.lastname: Bakker
authors.affiliation: Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, the Leggett Building, Guildford, GU2 7WG, Surrey, UK.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Manders
authors.affiliation: Laboratory for Myology, Move Research Institute Amsterdam, Faculty of Behavioural and Movement Sciences, VU University Amsterdam, Van der Boechorststraat 9, 1081 BA, Amsterdam, The Netherlands.
authors.forename: Annelies
authors.initials: A
authors.lastname: Pletsers
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Place Pierre de Coubertin 1, 1348, Louvain-la-Neuve, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Francaux
authors.affiliation: Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Gustav Mahlerlaan 3004, 1081 LA, Amsterdam, The Netherlands.
authors.forename: Jenneke
authors.initials: J
authors.lastname: Klein-Nulend
authors.affiliation: Laboratory for Myology, Move Research Institute Amsterdam, Faculty of Behavioural and Movement Sciences, VU University Amsterdam, Van der Boechorststraat 9, 1081 BA, Amsterdam, The Netherlands.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Jaspers
authors.affiliation: Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Tervuursevest 101, Box 1500, 3001, Leuven, Belgium; Institute of Neuroscience, Université catholique de Louvain, Place Pierre de Coubertin 1, 1348, Louvain-la-Neuve, Belgium. Electronic address: louise.deldicque@uclouvain.be.
authors.forename: Louise
authors.initials: L
authors.lastname: Deldicque
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D004721:Endoplasmic Reticulum / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000502:physiology*; D009929:Organ Size / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D009124:Muscle Proteins
keywords: Leucine; S6K1; Sarcopenia; Tunicamycin; Unfolded protein response