Age-related differences in the dose-response relationship of muscle protein synthesis to resistance exercise in young and old men

Abstract

We investigated how myofibrillar protein synthesis (MPS) and muscle anabolic signalling were affected by resistance exercise at 20-90% of 1 repetition maximum (1 RM) in two groups (25 each) of post-absorptive, healthy, young (24 +/- 6 years) and old (70 +/- 5 years) men with identical body mass indices (24 +/- 2 kg m(-2)). We hypothesized that, in response to exercise, anabolic signalling molecule phosphorylation and MPS would be modified in a dose-dependant fashion, but to a lesser extent in older men. Vastus lateralis muscle was sampled before, immediately after, and 1, 2 and 4 h post-exercise. MPS was measured by incorporation of [1,2-(13)C] leucine (gas chromatography-combustion-mass spectrometry using plasma [1,2-(13)C]alpha-ketoisocaparoate as surrogate precursor); the phosphorylation of p70 ribosomal S6 kinase (p70s6K) and eukaryotic initiation factor 4E binding protein 1 (4EBP1) was measured using Western analysis with anti-phosphoantibodies. In each group, there was a sigmoidal dose-response relationship between MPS at 1-2 h post-exercise and exercise intensity, which was blunted (P < 0.05) in the older men. At all intensities, MPS fell in both groups to near-basal values by 2-4 h post-exercise. The phosphorylation of p70s6K and 4EBP1 at 60-90% 1 RM was blunted in older men. At 1 h post-exercise at 60-90% 1 RM, p70s6K phosphorylation predicted the rate of MPS at 1-2 h post-exercise in the young but not in the old. The results suggest that in the post-absorptive state: (i) MPS is dose dependant on intensity rising to a plateau at 60-90% 1 RM; (ii) older men show anabolic resistance of signalling and MPS to resistance exercise.

Figure 1. Protocol for the measurement of the relationships of myofibrillar protein synthesis and muscle anabolic signal molecule phosphorylation

Each subject was studied over the period shown in the fasted state with 5 young and 5 older subjects carrying out exercise with their dominant leg randomly assigned to 20–90% 1 RM.

Figure 2. Dose–response relationship of myofibrillar protein synthesis (FSR, fractional synthetic rate,% h⁻¹) measured at 1–2 h post-exercise for 5 young men and 5 older men at each intensity

The responses of the young men overall were greater than those of the older men (P < 0.04). The responses between 60 and 90% of 1 RM in young and old were indistinguishable from each other but those in the young were together significantly higher than in the older men (P < 0.01) for 15 subjects in each group

Figure 3. Time course of the averaged responses to exercise at 60–90% 1 RM of myofibrillar protein synthesis (FSR, fractional synthetic rate,% h⁻¹) at 60–90% 1 RM for 15 subjects in each group of young and older subjects

*P < 0.05. Note that protein synthesis is measured over 2.5 h in the basal pre-exercise state and then over the periods shown post-exercise.

Figure 4. Time courses of the responses of phosphorylation of p70s6K and 4EBP1 (arbitrary units as percentage basal for each subject) averaged for intensities of 60–90% 1 RM

n= 15 in each group. *P < 0.05.

Figure 5. Relationship between myofibrillar synthetic rate and extent of phosphorylation of p70s6K averaged for responses at 60–90% in young subjects (above) and older subjects (below)

There was a significant relationship (P= 0.049) between degree of phosphorylation (arbitrary units and protein synthetic rate (FSR,% h⁻¹) only in the young. Note: some points overlaid.