Chronic essential amino acid supplementation in the elderly increases basal muscle protein synthesis and S6K1 phosphorylation

Essential amino acids (EAA) stimulate muscle protein synthesis (MPS) via activation of the mTOR nutrient signaling pathway. mTOR signaling to its downstream effectors (S6K1 and 4E‐BP1) is an important regulator of translation initiation and MPS. We hypothesized that chronic EAA supplementation would increase basal MPS via the mTOR signaling pathway in healthy older subjects. Older men and women were randomized in a blinded fashion to receive either 15g EAA (n=6) (7.5g twice daily) or placebo (n=5) for three months. Muscle biopsies were taken from the v. lateralis in the postabsorptive state before and after 3 months for determination of the basal muscle fractional synthetic rate (FSR). Protein abundance and phosphorylation status of mTOR, S6K1, and 4E‐BP1 were determined by immunoblotting methods. Basal FSR increased after 3 months in the EAA group (0.060 ± 0.003 to 0.083 ± 0.004 %·h −1 , mean ± SEM, P<0.01) but not in the placebo group (0.055 ± 0.004 to 0.061 ± 0.004, %·h −1 ). There were no changes in mTOR or 4E‐BP1 protein abundance or phosphorylation status after 3‐months in either group. However, phosphorylation status of S6K1(Thr389) increased 2‐fold in the EAA group after 3‐months (P<0.05). S6K1 phosphorylation remained unchanged in the placebo group. These preliminary results suggest that daily EAA supplementation in older men and women increases the basal rate of MPS through enhanced mTOR signaling to S6K1. This project was funded by NIH/NIA R01 AG21539 to M. Sheffield‐Moore and P60 AG17231 to J.S. Goodwin and R.J. Urban. Studies were conducted on the GCRC at UTMB and funded by grant M01 RR 00073 from the National Center for Research Resources, NIH, USPHS