Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans

The molecular transducers of benefits from different exercise modalities remain incompletely defined. Here we report that 12 weeks of high-intensity aerobic interval (HIIT), resistance (RT), and combined exercise training enhanced insulin sensitivity and lean mass, but only HIIT and combined training improved aerobic capacity and skeletal muscle mitochondrial respiration. HIIT revealed a more robust increase in gene transcripts than other exercise modalities, particularly in older adults, although little overlap with corresponding individual protein abundance was noted. HIIT reversed many age-related differences in the proteome, particularly of mitochondrial proteins in concert with increased mitochondrial protein synthesis. Both RT and HIIT enhanced proteins involved in translational machinery irrespective of age. Only small changes of methylation of DNA promoter regions were observed. We provide evidence for predominant exercise regulation at the translational level, enhancing translational capacity and proteome abundance to explain phenotypic gains in muscle mitochondrial function and hypertrophy in all ages. [Display omitted] •High-intensity interval training improved age-related decline in muscle mitochondria•Training adaptations occurred with increased gene transcripts and ribosome proteins•Changes to RNA with training had little overlap with corresponding protein abundance•Enhanced ribosomal abundance and protein synthesis explain gains in mitochondria Robinson et al. assessed the effects of three different exercise modalities on skeletal muscle adaptations in young and older adults. While all enhanced insulin sensitivity, only HIIT and combined training improved aerobic capacity, associated with enhanced translation of mitochondrial proteins. HIIT effectively improved cardio-metabolic health parameters in aging adults.