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Anabolic resistance assessed by oral stable isotope ingestion following bed rest in young and older adult volunteers: Relationships with changes in muscle mass

Biolo, Gianni, Pišot, Rado, Mazzucco, Sara, Di Girolamo, Filippo Giorgio, Situlin, Roberta, Lazzer, Stefano, Grassi, Bruno, Reggiani, Carlo, Passaro, Angelina, Rittweger, Joern, Gasparini, Mladen, Šimunič, Boštjan, Narici, Marco
Clinical nutrition 2017 v.36 pp. 1420-1426
absorption, group behavior, hydroxylation, ingestion, magnetic resonance imaging, males, muscles, phenylalanine, protein synthesis, sarcopenia, stable isotopes, tyrosine
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.