Molecular Networks of Human Muscle Adaptation to Exercise and Age

Abstract

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 co-varied with gain in lean mass, we identified rapamycin (mTOR) signaling associating with growth (P = 1.4×10−30). 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-trans-retinoic acid (ATRA, Z-score = 4.5; P = 6×10−13) and inhibited aryl-hydrocarbon receptor signaling (AhR, Z-score = −2.3; P = 3×10−7)) 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 gene-expression 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 post-transcriptional processes (P = 1×10−6) 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.

Heterogeneity in resistance training-induced muscle strength and mass responses in men and women of different ages

“…In previous studies with healthy human subjects, e.g., several genetic variations (Riechman et al 2004;Devaney et al 2009;Walsh et al 2012;Van Deveire et al 2012), differences in skeletal muscle gene Raue et al 2012;Phillips et al 2013) and microRNA expression (Davidsen et al 2011), phosphorylation status of signaling proteins (Mayhew et al 2011;Mitchell et al 2013), androgen receptor concentrations (Ahtiainen et al 2011;Mitchell et al 2013), and satellite cell count (Petrella et al 2008) have been suggested to segregate high and low responders to RTinduced muscle hypertrophy. The physiological aspects of individual variation in phenotype responses to RT are apparently very complex phenomena and more studies specifically focused on high and low responders are required to reveal unambiguously the mechanisms of individual differences in RT-induced adaptations.…”

“…The robust study of individual responses to unilateral upper arm RT by Hubal et al (2005) showed that of 585 subjects, approximately 6 % showed practically no gains in muscle size. Also, other RT studies have reported that, in some subjects, muscle size gains are either minimal or non-existent following a training period Davidsen et al 2011;Raue et al 2012;Mitchell et al 2013;Phillips et al 2013). Similarly to muscle size responses, gains in muscle strength during RT are also highly individual (Hubal et al 2005;Erskine et al 2010).…”

Performance trade-offs and individual quality in decathletes

“…For example, recent work on the genetic predictors of the individual response to training in humans suggests the presence of networks of muscle-plasticity genes that affect the ability of muscle to remodel. These networks are activated in the same way in both resistance and endurance training (Timmons, 2011;Phillips et al, 2013). If these plasticity networks have large magnitude effects on performance, we would expect some individuals to excel in both highpower and high-endurance events and some to perform poorly in both types of events, even if all athletes had precisely the same training.…”

Examinat?on of healthy lifestyle attitudes of physical education and sports teaching department students

“…Egzersiz, soluk alıp verme hızını, derinliğini ve kalp atış hızını belirli bir oranda artıran, az da olsa terlemeye yol açan, kollar ve bacaklar gibi büyük kas gruplarıyla yapılan bazal düzeyin üzerinde enerji harcamayı gerektiren bedensel hareketlerdir 8,9 . Her geçen gün insan sağlığında egzersizin rolü ile ilgili yayınlar artmakta ve bazı hastalıkların önlenmesinde, kardiovasküler hastalık, osteoporozis, bazı kanserler ve bazı mental bozukluklar 10 tedavisinde ve hatta yaşlılığın geciktirilmesinde egzersizin oynadığı rol daha belirgin hale gelmektedir 11. Yaşlanma; kas kaybı, fiziksel hareketsizlik ve güçsüzlüğün artmasıyla karakterize olmaktadır 12 . Sağlıklı diyet ve egzersiz alışkanlığı, sağlıklı yaşlanmaya katkıda bulunarak egzersizin oynadığı rolün önemini ortaya koymaktadır.…”