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

Resistance exercise training (RET) is one of the most effective strategies for preventing declines in skeletal muscle mass and strength with age. Hypertrophic responses to RET with age are diminished compared to younger individuals. In response to 6weeks RET, we found blunted hypertrophic responses with age are underpinned by chronic deficits in long-term muscle protein synthesis. We show this is likely to be the result of multifactorial deficits in anabolic hormones and blunted translational efficiency and capacity. These results provide great insight into age-related exercise adaptations and provide a platform on which to devise appropriate nutritional and exercise interventions on a longer term basis. AbstractAgeing is associated with impaired hypertrophic responses to resistance exercise training (RET). Here we investigated the aetiology of anabolic resistance' in older humans. Twenty healthymale individuals, 10 younger (Y; 231years) and 10 older (O; 693years), performed 6weeks unilateral RET (6x8 repetitions, 75% of one repetition maximum (1-RM), 3times per week). After baseline bilateral vastus lateralis (VL) muscle biopsies, subjects consumed 150ml D2O (70atom%; thereafter 50mlweek(-1)), further bilateral VL muscle biopsies were taken at 3 and 6weeks to quantify muscle protein synthesis (MPS) via gas chromatography-pyrolysis-isotope ratio mass spectrometry. After RET, 1-RM increased in Y (+354%) and O (+253%; P<0.01), while MVC increased in Y (+215%; P<0.01) but not O (+63%; not significant (NS)). In comparison to Y, O displayed blunted RET-induced increases in muscle thickness (at 3 and 6weeks, respectively, Y: +8 +/- 1% and +11 +/- 2%, P<0.01; O: +2.6 +/- 1% and +3.5 +/- 2%, NS). While basal' longer term MPS was identical between Y and O (approximate to 1.35 +/- 0.1%day(-1)), MPS increased in response to RET only in Y (3weeks, Y: 1.61 +/- 0.1%day(-1); O: 1.49 +/- 0.1%day(-1)). Consistent with this, O exhibited inferior ribosomal biogenesis (RNA:DNA ratio and c-MYC induction: Y: +4 +/- 2 fold change; O: +1.9 +/- 1 fold change), translational efficiency (S6K1 phosphorylation, Y: +10 +/- 4 fold change; O: +4 +/- 2 fold change) and anabolic hormone milieu (testosterone, Y: 367 +/- 19; O: 274 +/- 19ngdl(-1) (all P<0.05). Anabolic resistance is thus multifactorial. Resistance exercise training (RET) is one of the most effective strategies for preventing declines in skeletal muscle mass and strength with age. Hypertrophic responses to RET with age are diminished compared to younger individuals. In response to 6weeks RET, we found blunted hypertrophic responses with age are underpinned by chronic deficits in long-term muscle protein synthesis. We show this is likely to be the result of multifactorial deficits in anabolic hormones and blunted translational efficiency and capacity. These results provide great insight into age-related exercise adaptations and provide a platform on which to devise appropriate nutritional and exercise interventions on a longer term basis.