Synchronous deficits in cumulative muscle protein synthesis and ribosomal biogenesis underlie age-related anabolic resistance to exercise in humans.

Abstract

Aging is associated with impaired hypertrophic responses to resistance exercise training (RET). Here we investigated the aetiology of "anabolic resistance" in older humans. Twenty healthy male individuals (10 younger (Y: 23 ± 1y)), 10 older (O: 69 ± 3y)) performed 6-wks unilateral RET (6×8 repetition, 75%-1RM 3.wk(-1) ). After baseline bilateral vastus lateralis (VL) muscle biopsies, subjects consumed 150 ml D2 O (70-Atom%; thereafter 50ml·wk(-1) ), further bilateral VL muscle biopsies were taken at 3-and-6-weeks to quantify muscle protein synthesis (MPS) via gas chromatography-pyrolysis-isotope-ratio mass spectrometry. After RET, 1-RM increased in Y: +35 ± 4% and O: +25 ± 3% (P < 0.01), while MVC increased in Y: +21 ± 5% (P < 0.01) but not O: +6 ± 3% (P = NS). In comparison to Y, O displayed blunted RET-induced increases in muscle thickness (Y: +8 ± 1% and +11 ± 2% (P < 0.01) vs. O: +2.6 ± 1% and +3.5 ± 2%, (P = NS) at 3 and 6-wks, respectively). While "basal" longer-term MPS was identical between Y and O (∼1.35 ± 0.1%d(-1) ), MPS increased in response to RET only in Y (3-wks Y: 1.61 ± 0.1%.d(-1 ) vs. O: 1.49 ± 0.1%.d(-1) ). Consistent with this, O exhibited inferior ribosomal biogenesis (RNA:DNA-ratio and c-MYC induction, Y: +4 ± 2 vs. O: +1.9 ± 1), translational efficiency (S6K1 phosphorylation Y: +10 ± 4 vs. O: +4 ± 2) and anabolic hormone milieu (testosterone Y: 367 ± 19 vs. O: 274 ± 19 ng dl(-1) (all P < 0.05). Anabolic resistance is thus, multifactorial.