title: Anabolic resistance assessed by oral stable isotope ingestion following bed rest in young and older adult volunteers: Relationships with changes in muscle mass.
abstract: Aging and experimental bed rest are associated with muscle atrophy and resistance to post-prandial stimulation of protein synthesis or anabolic resistance (AR). We have used in young and older adult volunteers, during short-term bed rest, a quick and non-invasive method, based on a single oral bolus of the stable isotope L[ring-2H5]phenylalanine (D5Phe), to determine post-prandial AR, defined as ratio between irreversible hydroxylation and incorporation into body protein of ingested phenylalanine.
  
  
  
  We compared in older (O, 59 ± 1 y) and young (Y, 23 ± 1 y) healthy male volunteers the effects of two-week bed rest on post-prandial protein kinetics, assessed during absorption of a standard ready-to-use oral nutritional supplement, through stable-labeled isotope amino acid D5Phe, diluted in water, given as single oral load. The metabolic fate of D5Phe is either utilization for protein synthesis or irreversible hydroxylation to L[ring-2H4]tyrosine (D4Tyr). AR was defined as ratio between the areas under the curves of D4Tyr-to-D5Phe plasma concentrations over 6 h meal absorption. To determine the relationships between AR and muscle changes following bed rest, quadriceps muscle volume (QMV) was determined by magnetic resonance imaging (MRI).
  
  
  
  At baseline, in pooled Y and O subjects, values of AR were inversely correlated with QMV (R = -0.75; p < 0.03). Following 2-weeks of inactivity, there were significant bed rest effects on AR (p < 0.01) and QMV (p < 0.03), as well as significant bed rest × group interaction for AR (p < 0.03; +9.2% in Y; +21.9% in O) and QMV (p < 0.05; -5.7% in Y; -%7.3 in O). In pooled subjects, the percentage delta changes in AR and QMV, induced by bed rest, were inversely correlated (R = -0.57; p < 0.05).
  
  
  
  Bed rest-induced AR is much greater in the older than in younger adults. We have developed a new, simple, non-invasive method for the assessment of AR. The results indicate that this metabolic abnormality is a key mechanism for sarcopenia of aging and inactivity.
authors.affiliation: Department of Medical, Surgical and Health Sciences, Clinica Medica AOUTS, University of Trieste, Italy. Electronic address: biolo@units.it.
authors.forename: Gianni
authors.initials: G
authors.lastname: Biolo
authors.affiliation: Institute for Kinesiology Research, Science and Research Center of Koper, University of Primorska, Koper, Slovenia.
authors.forename: Rado
authors.initials: R
authors.lastname: Pišot
authors.affiliation: Department of Medical, Surgical and Health Sciences, Clinica Medica AOUTS, University of Trieste, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Mazzucco
authors.affiliation: Department of Medical, Surgical and Health Sciences, Clinica Medica AOUTS, University of Trieste, Italy.
authors.forename: Filippo Giorgio
authors.initials: FG
authors.lastname: Di Girolamo
authors.affiliation: Department of Medical, Surgical and Health Sciences, Clinica Medica AOUTS, University of Trieste, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Situlin
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Lazzer
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Grassi
authors.affiliation: Department of Biomedical Sciences, University of Padua, Padua, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Reggiani
authors.affiliation: Department of Medical Sciences, Section of Internal and Cardiorespiratory Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Angelina
authors.initials: A
authors.lastname: Passaro
authors.affiliation: Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany.
authors.forename: Joern
authors.initials: J
authors.lastname: Rittweger
authors.affiliation: Department of Vascular Surgery, General Hospital Izola, Izola, Slovenia.
authors.forename: Mladen
authors.initials: M
authors.lastname: Gasparini
authors.affiliation: Institute for Kinesiology Research, Science and Research Center of Koper, University of Primorska, Koper, Slovenia.
authors.forename: Boštjan
authors.initials: B
authors.lastname: Šimunič
authors.affiliation: MRC/ARUK Centre for Musculoskeletal Ageing Research, University of Nottingham, Derby Royal Hospital, Derby, United Kingdom.
authors.forename: Marco
authors.initials: M
authors.lastname: Narici
mesh_terms: D000375:Aging; D001510:Bed Rest / Q000009:adverse effects*; D015992:Body Mass Index; D016022:Case-Control Studies; D006801:Humans; D007554:Isotopes / Q000032:analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009133:Muscular Atrophy / Q000097:blood* / Q000175:diagnosis; D010649:Phenylalanine / Q000008:administration & dosage / Q000032:analysis; D019518:Postprandial Period; D014176:Protein Biosynthesis; D055815:Young Adult
chemical_list: D007554:Isotopes; D009124:Muscle Proteins; D010649:Phenylalanine
keywords: Aging; Anabolic resistance; Bed rest; Isotopic tracers; Muscle atrophy; Skeletal muscle