Correction: Molecular Networks of Human Muscle Adaptation to Exercise and Age

Physical activity and molecular ageing presumably interact to precipitate musculoskeletal decline in humans with age.Herein, we have delineated molecular networks for these two major components of sarcopenic risk using multiple independent clinical cohorts.We generated genome-wide transcript profiles from individuals (n = 44) who then undertook 20 weeks of supervised resistance-exercise training (RET).Expectedly, our subjects exhibited a marked range of hypertrophic responses (3% to +28%), and when applying Ingenuity Pathway Analysis (IPA) up-stream analysis to ,580 genes that covaried with gain in lean mass, we identified rapamycin (mTOR) signaling associating with growth (P = 1.4610 230 ).Paradoxically, those displaying most hypertrophy exhibited an inhibited mTOR activation signature, including the striking down-regulation of 70 rRNAs.Differential analysis found networks mimicking developmental processes (activated all-transretinoic acid (ATRA, Z-score = 4.5; P = 6610 213 ) and inhibited aryl-hydrocarbon receptor signaling (AhR, Z-score = 22.3; P = 3610 27 )) with RET.Intriguingly, as ATRA and AhR gene-sets were also a feature of endurance exercise training (EET), they appear to represent ''generic'' physical activity responsive gene-networks.For age, we found that differential geneexpression methods do not produce consistent molecular differences between young versus old individuals.Instead, utilizing two independent cohorts (n = 45 and n = 52), with a continuum of subject ages (18-78 y), the first reproducible set of age-related transcripts in human muscle was identified.This analysis identified ,500 genes highly enriched in posttranscriptional processes (P = 1610 26 ) and with negligible links to the aforementioned generic exercise regulated gene-sets and some overlap with ribosomal genes.The RNA signatures from multiple compounds all targeting serotonin, DNA topoisomerase antagonism, and RXR activation were significantly related to the muscle age-related genes.Finally, a number of specific chromosomal loci, including 1q12 and 13q21, contributed by more than chance to the age-related gene list (P = 0.01-0.005),implying possible epigenetic events.We conclude that human muscle age-related molecular processes appear distinct from the processes regulated by those of physical activity.