Age-related differences in dose response of muscle protein synthesis to resistance exercise in young and old men.Kumar V, Selby A, Rankin D, Patel R, Atherton P, Hildebrandt W, Williams J, Smith K, Seynnes O, Hiscock N, Rennie MJ. University of Nottingham, School of Graduate Entry Medicine and Health, Derby, DE22 3DT. We investigated how myofibrillar protein synthesis and muscle anabolic signalling were affected by resistance exercise at 20-90% of 1 repetition maximum (1 RM) in two groups of 25 each, postabsorptive, healthy, young (24+/-6 y) and old (70+/-5 y) 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 postabsorptive 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. A very interesting study with some very interesting results. The subjects exercised with their dominant legs at randomly assigned intensities from 20% to 90% 1RM, 5 subjects per group. They performed seated unilateral leg extensions and flexions (1-2 s each) with 2 min rest between sets. They used this tempo to as closely as possible keep the volume of exercise i.e. the force × time-under-tension product (often described as “work”) equal. IOW % 1 RM × number of repetitions × number of sets so if 1RM was 100lbs 20% 3 sets × 27 reps = 1620 Arbitrary Work units 40%, 3 sets × 14 reps = 1680 60%, 3 sets × 9 reps = 1620 75%, 3 sets × 8 reps = 1800 90%, 6 sets × 3 reps. = 1620 Total work output (i.e. was 1620 to 1800 units at different exercise intensities, and total time-under-tension was obtained by multiplying by 4 s.) Now for the interesting part. At intensities up to 60% the response was graded and reflected well with the increases in intensity. Between 60% and 90% of 1RM the response was about equal. Indicating that, in the untrained, myofibrillar PS response is intensity dependant to a point. But once at a point of adeqaute recruitment and activation the response is about equal. Some drawbacks or rather areas that could be examined further. What would happen if the intensities below 60% were increased in their force/volume, ie more sets taken nearer to failure so recruitement and fiber activation were matched versus just external work? My guess is that PS would be higher than what was seen here. What would happen with advanced trainees? Since they used relative intensity I would venture to guess that as the relative RM increases and if novel enough of a stimulus the PS response would still be manifest. (see my earlier posts in this forum) What would happen if say they added more work in the higher intensity? Say they added another set in 90% 1RM, would it still equal the 60% 1rm in response magnitude, changing the AUC? My guess is maybe maybe not as it may be a matter of once a threshold in force/volume is hit then doing more would not add any additional benefit. Now the other aspect of this study was too compare the difference between young and old. Without great detail or commentary the young showed a significantly higher response but that is nothing new. Yet the old still showed that intensity dependancy correlated.