Cited by 199Muscle Physiology and DisordersGenetics and Physical PerformanceNutrition and Health in Aging

The DOI matches its Crossref record; 90 of the 90 references it cites were found in a registry or an index.

Molecular Networks of Human Muscle Adaptation to Exercise and Age

Open access

Phillips, Bethan E., Williams, John P., Gustafsson, Thomas, Bouchard, Claude, Rankinen, Tuomo, Knudsen, Steen, Smith, Kenneth, Timmons, James A., Atherton, Philip J.·2013·PLoS Genetics

DOI 10.1371/journal.pgen.1003389PMC PMC3605101

Open this paper in CoChat — free account Open PDF

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1371/journal.pgen.1003389

Cites

90 of 90 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

In silico prediction of protein-protein interactions in human macrophages
Souiai, O., Guerfali, F. Z., Miled, S. B., Brun, C., & Benkahla, A. (2014) · BMC Research Notes · doi:10.1186/1756-0500-7-157 · Cited by 10,785
Significance analysis of microarrays applied to the ionizing radiation response
Tusher, V. G., Tibshirani, R., & Chu, G. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.091062498 · Cited by 10,568
The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease
Lamb, J., Crawford, E. D., Peck, D., Modell, J. W., Blat, I. C., Wrobel, M. J., Lerner, J., Brunet, J.-P., Subramanian, A., Ross, K. N., et al. (2006) · Science · doi:10.1126/science.1132939 · Cited by 5,257
Network pharmacology: the next paradigm in drug discovery
Hopkins, A. L. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.118 · Cited by 4,622
Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability
Janssen, I., Heymsfield, S. B., & Ross, R. (2002) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2002.50216.x · Cited by 3,139 · cited 1×
“As the number of people living beyond their eighth decade rises, it is expected that skeletal muscle atrophy and dysfunction (sarcopenia and dynapenia respectively) will become an increasing public health challenge [73].”
Background
The genetics of ageing
Kenyon, C. J. (2010) · Nature · doi:10.1038/nature08980 · Cited by 2,739
Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways
Rommel, C., Bodine, S. C., Clarke, B. A., Rossman, R., Nunez, L., Stitt, T. N., Yancopoulos, G. D., & Glass, D. J. (2001) · Nature Cell Biology · doi:10.1038/ncb1101-1009 · Cited by 1,583
Navigating chemical space for biology and medicine
Lipinski, C. A., & Hopkins, A. L. (2004) · Nature · doi:10.1038/nature03193 · Cited by 1,028
Appendicular skeletal muscle mass: effects of age, gender, and ethnicity
Gallagher, D., Visser, M., De Meersman, R. E., Sepúlveda, D., Baumgartner, R. N., Pierson, R. N., Harris, T., & Heymsfield, S. B. (1997) · Journal of Applied Physiology · doi:10.1152/jappl.1997.83.1.229 · Cited by 966
Age‐related differences in the dose–response relationship 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., et al. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2008.164483 · Cited by 740 · cited 1×
“Many exogenous factors may influence RET-induced hypertrophy including manipulation of exercise volume [7], intensity [8] and adequate macronutrient availability [9] all of which interact with an individual’s genotype to determine muscle growth.”
BackgroundSelf-citation

Flagged first, then by citations

Show all 90 references

Sorted by citations

Limb proportions show developmental plasticity in response to embryo movement
Pollard, A. S., Charlton, B., Hutchinson, J. R., Gustafsson, T. P., McGonnell, I. M., Timmons, J. A., & Pitsillides, A. A. (2017) · Scientific Reports · doi:10.1038/srep41926 · Cited by 2,377
Self-citation
Adaptations to Endurance and Strength TrainingPreprint
Hughes, D. C., Ellefsen, S., & Baar, K. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029769 · Cited by 661
Transcriptomic profiling of skeletal muscle adaptations to exercise and inactivity
Pillon, N. J., Gabriel, B. M., Dollet, L., Smith, J. A. B., Sardón Puig, L., Botella, J., Bishop, D. J., Krook, A., & Zierath, J. R. (2020) · Nature Communications · doi:10.1038/s41467-019-13869-w · Cited by 457
Sarcopenia, frailty and their prevention by exercise
Nascimento, C. M., Ingles, M., Salvador-Pascual, A., Cominetti, M. R., Gomez-Cabrera, M. C., & Viña, J. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.08.035 · Cited by 396
Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities
Migliavacca, E., Tay, S. K. H., Patel, H. P., Sonntag, T., Civiletto, G., McFarlane, C., Forrester, T., Barton, S. J., Leow, M. K., Antoun, E., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13694-1 · Cited by 365
Concurrent exercise training: do opposites distract?
Coffey, V. G., & Hawley, J. A. (2017) · The Journal of Physiology · doi:10.1113/jp272270 · Cited by 351
Interference between concurrent resistance and endurance exercise: Molecular bases and the role of individual training variables
Fyfe, J. J., Bishop, D. J., & Stepto, N. K. (2014) · Sports Medicine · doi:10.1007/s40279-014-0162-1 · Cited by 347
There Are No Nonresponders to Resistance-Type Exercise Training in Older Men and Women
Churchward‐Venne, T. A., Tieland, M., Verdijk, L. B., Leenders, M., Dirks, M. L., de Groot, C. P. G. M., & van Loon, L. J. C. (2015) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2015.01.071 · Cited by 308
A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status
Sood, S., Gallagher, I. J., Lunnon, K., Rullman, E., Keohane, A., Crossland, H., Phillips, B. E., Cederholm, T., Jensen, T., van Loon, L. J. C., et al. (2015) · Genome biology · doi:10.1186/s13059-015-0750-x · Cited by 240
Self-citation
Discovery proteomics in aging human skeletal muscle finds change in spliceosome, immunity, proteostasis and mitochondria
Ubaida‐Mohien, C., Lyashkov, A. E., González‐Freire, M., Tharakan, R., Shardell, M. D., Moaddel, R., Semba, R. D., Chia, C. W., Gorospe, M., Sen, R., et al. (2019) · eLife · doi:10.7554/elife.49874 · Cited by 234
Heterogeneity in resistance training-induced muscle strength and mass responses in men and women of different ages
Ahtiainen, J. P., Walker, S., Peltonen, H., Holviala, J., Sillanpää, E., Karavirta, L., Sallinen, J., Mikkola, J., Valkeinen, H., Mero, A., et al. (2016) · AGE · doi:10.1007/s11357-015-9870-1 · Cited by 231
Reduced resting skeletal muscle protein synthesis is rescued by resistance exercise and protein ingestion following short-term energy deficit
Areta, J. L., Burke, L. M., Camera, D. M., West, D. W. D., Crawshay, S., Moore, D. R., Stellingwerff, T., Phillips, S. M., Hawley, J. A., & Coffey, V. G. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00590.2013 · Cited by 227
Machine Learning on Human Muscle Transcriptomic Data for Biomarker Discovery and Tissue-Specific Drug Target Identification
Mamoshina, P., Volosnikova, M., Ozerov, I. V., Lane, E., Skibina, E., Cortese, F., & Zhavoronkov, A. A. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00242 · Cited by 231
Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions
Roberts, M. D., McCarthy, J. J., Hornberger, T. A., Phillips, S. M., Mackey, A. L., Nader, G. A., Boppart, M. D., Kavazis, A. N., Reidy, P. T., Ogasawara, R., et al. (2023) · Physiological Reviews · doi:10.1152/physrev.00039.2022 · Cited by 214
Post-exercise cold water immersion attenuates acute anabolic signalling and long-term adaptations in muscle to strength training
Roberts, L. A., Raastad, T., Markworth, J. F., Figueiredo, V. C., Egner, I. M., Shield, A., Cameron‐Smith, D., Coombes, J. S., & Peake, J. M. (2015) · The Journal of Physiology · doi:10.1113/jp270570 · Cited by 218
Acute Post-Exercise Myofibrillar Protein Synthesis Is Not Correlated with Resistance Training-Induced Muscle Hypertrophy in Young Men
Mitchell, C. J., Churchward-Venne, T. A., Parise, G., Bellamy, L., Baker, S. K., Smith, K., Atherton, P. J., & Phillips, S. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089431 · Cited by 212
Self-citation
Ribosome biogenesis: Emerging evidence for a central role in the regulation of skeletal muscle mass
Chaillou, T., Kirby, T. J., & McCarthy, J. J. (2014) · Journal of Cellular Physiology · doi:10.1002/jcp.24604 · Cited by 211
Skeletal muscle hypertrophy adaptations predominate in the early stages of resistance exercise training, matching deuterium oxide‐derived measures of muscle protein synthesis and mechanistic target of rapamycin complex 1 signaling
Brook, M. S., Wilkinson, D. J., Mitchell, W. K., Lund, J. N., Szewczyk, N. J., Greenhaff, P. L., Smith, K., & Atherton, P. J. (2015) · The FASEB Journal · doi:10.1096/fj.15-273755 · Cited by 206
Self-citation
Skeletal muscle homeostasis and plasticity in youth and ageing: impact of nutrition and exercise
Brook, M. S., Wilkinson, D. J., Phillips, B. E., Pérez‐Schindler, J., Philp, A., Smith, K., & Atherton, P. J. (2015) · Acta Physiologica · doi:10.1111/apha.12532 · Cited by 214
Self-citation
Mitochondria, Muscle Health, and Exercise with Advancing Age
Carter, H. N., Chen, C. C. W., & Hood, D. A. (2015) · Physiology · doi:10.1152/physiol.00039.2014 · Cited by 191
Muscular and Systemic Correlates of Resistance Training-Induced Muscle Hypertrophy
Mitchell, C. J., Churchward‐Venne, T. A., Bellamy, L. M., Parise, G., Baker, S. K., & Phillips, S. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078636 · Cited by 193
Biochemical Pathways of Sarcopenia and Their Modulation by Physical Exercise: A Narrative Review
Ziaaldini, M. M., Marzetti, E., Picca, A., & Murlasits, Z. (2017) · Frontiers in Medicine · doi:10.3389/fmed.2017.00167 · Cited by 178
Ribosome biogenesis may augment resistance training-induced myofiber hypertrophy and is required for myotube growth in vitro
Stec, M. J., Kelly, N. A., Many, G. M., Windham, S. T., Tuggle, S. C., & Bamman, M. M. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00486.2015 · Cited by 161
The Acute Satellite Cell Response and Skeletal Muscle Hypertrophy following Resistance Training
Bellamy, L. M., Joanisse, S., Grubb, A., Mitchell, C. J., McKay, B. R., Phillips, S. M., Baker, S., & Parise, G. (2014) · PLoS ONE · doi:10.1371/journal.pone.0109739 · Cited by 149
Acute resistance exercise activates rapamycin‐sensitive and ‐insensitive mechanisms that control translational activity and capacity in skeletal muscle
West, D. W. D., Baehr, L. M., Marcotte, G. R., Chason, C. M., Tolento, L., Gomes, A. V., Bodine, S. C., & Baar, K. (2015) · The Journal of Physiology · doi:10.1113/jp271365 · Cited by 152
An Evidence-Based Narrative Review of Mechanisms of Resistance Exercise–Induced Human Skeletal Muscle Hypertrophy
LIM, C., NUNES, E. A., CURRIER, B. S., MCLEOD, J. C., THOMAS, A. C. Q., & PHILLIPS, S. M. (2022) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002929 · Cited by 142
Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity
ROWLANDS, D. S., Page, R., Sukala, W. R., Giri, M., Ghimbovschi, S. D., Hayat, I., Cheema, B. S., Lys, I., Leikis, M. J., Sheard, P., et al. (2014) · Physiological Genomics · doi:10.1152/physiolgenomics.00024.2014 · Cited by 144
Skeletal muscle and resistance exercise training; the role of protein synthesis in recovery and remodeling
McGlory, C., Devries, M. C., & Phillips, S. M. (2017) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00613.2016 · Cited by 135
Comparative Transcriptome and Methylome Analysis in Human Skeletal Muscle Anabolism, Hypertrophy and Epigenetic Memory
Turner, D. C., Seaborne, R. A. E., & Sharples, A. P. (2019) · Scientific Reports · doi:10.1038/s41598-019-40787-0 · Cited by 135
The Importance of Resistance Exercise Training to Combat Neuromuscular Aging
Lavin, K. M., Roberts, B. M., Fry, C. S., Moro, T., Rasmussen, B. B., & Bamman, M. M. (2019) · Physiology · doi:10.1152/physiol.00044.2018 · Cited by 134
Exercise and the Regulation of Endocrine Hormones
Hackney, A. C., & Lane, A. R. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.07.001 · Cited by 140
Resistance exercise training modulates acute gene expression during human skeletal muscle hypertrophy
Nader, G. A., von Walden, F., Liu, C., Lindvall, J., Gutmann, L., Pistilli, E. E., & Gordon, P. M. (2014) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01366.2013 · Cited by 129
Exercise-induced skeletal muscle signaling pathways and human athletic performance
Camera, D. M., Smiles, W. J., & Hawley, J. A. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.02.007 · Cited by 128
Role of Ingested Amino Acids and Protein in the Promotion of Resistance Exercise–Induced Muscle Protein Anabolism
Reidy, P. T., & Rasmussen, B. B. (2016) · The Journal of Nutrition · doi:10.3945/jn.114.203208 · Cited by 128
Skeletal muscle transcriptome in healthy aging
Tumasian, R. A., Harish, A., Kundu, G., Yang, J.-H., Ubaida-Mohien, C., Gonzalez-Freire, M., Kaileh, M., Zukley, L. M., Chia, C. W., Lyashkov, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22168-2 · Cited by 126
Overexpression of the vitamin D receptor (VDR) induces skeletal muscle hypertrophy
Bass, J. J., Nakhuda, A., Deane, C. S., Brook, M. S., Wilkinson, D. J., Phillips, B. E., Philp, A., Tarum, J., Kadi, F., Andersen, D. K., et al. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101059 · Cited by 121
Self-citation
Time trajectories in the transcriptomic response to exercise - a meta-analysis
Amar, D., Lindholm, M. E., Norrbom, J., Wheeler, M. T., Rivas, M. A., & Ashley, E. A. (2021) · Nature Communications · doi:10.1038/s41467-021-23579-x · Cited by 104
The Molecular Basis for Load-Induced Skeletal Muscle Hypertrophy
Marcotte, G. R., West, D. W. D., & Baar, K. (2014) · Calcified Tissue International · doi:10.1007/s00223-014-9925-9 · Cited by 123
Physiological Differences Between Low Versus High Skeletal Muscle Hypertrophic Responders to Resistance Exercise Training: Current Perspectives and Future Research Directions
Roberts, M. D., Haun, C. T., Mobley, C. B., Mumford, P. W., Romero, M. A., Roberson, P. A., Vann, C. G., & McCarthy, J. J. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00834 · Cited by 107
Kynurenine signaling through the aryl hydrocarbon receptor: Implications for aging and healthspan
Kaiser, H., Parker, E. J., & Hamrick, M. W. (2019) · Experimental Gerontology · doi:10.1016/j.exger.2019.110797 · Cited by 107
Impact of Physical Activity and Exercise on the Epigenome in Skeletal Muscle and Effects on Systemic Metabolism
Plaza‐Díaz, J., Izquierdo, D., Torres‐Martos, Á., Baig, A. T., Aguilera, C. M., & Ruiz‐Ojeda, F. J. (2022) · Biomedicines · doi:10.3390/biomedicines10010126 · Cited by 121
Focal adhesion kinase is required for IGF-I-mediated growth of skeletal muscle cells via a TSC2/mTOR/S6K1-associated pathway
Crossland, H., Kazi, A. A., Lang, C. H., Timmons, J. A., Pierre, P., Wilkinson, D. J., Smith, K., Szewczyk, N. J., & Atherton, P. J. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00541.2012 · Cited by 95
Self-citation
Blunted hypertrophic response in aged skeletal muscle is associated with decreased ribosome biogenesis
Kirby, T. J., Lee, J. D., England, J. H., Chaillou, T., Esser, K. A., & McCarthy, J. J. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00296.2015 · Cited by 89
Swimming-induced exercise promotes hypertrophy and vascularization of fast skeletal muscle fibres and activation of myogenic and angiogenic transcriptional programs in adult zebrafish
Palstra, A. P., Rovira, M., Rizo‐Roca, D., Torrella, J. R., Spaink, H. P., & Planas, J. V. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-1136 · Cited by 88
Skeletal Muscle Quality: A Biomarker for Assessing Physical Performance Capabilities in Young Populations
Naimo, M. A., Varanoske, A. N., Hughes, J. M., & Pasiakos, S. M. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.706699 · Cited by 87
Satellite Cell Depletion Disrupts Transcriptional Coordination and Muscle Adaptation to Exercise
Englund, D. A., Figueiredo, V. C., Dungan, C. M., Murach, K. A., Peck, B. D., Petrosino, J. M., Brightwell, C. R., Dupont, A., Neal, A. C., Fry, C. S., et al. (2020) · Function · doi:10.1093/function/zqaa033 · Cited by 84
Transcriptome response of human skeletal muscle to divergent exercise stimuli
Dickinson, J. M., D’Lugos, A. C., Naymik, M., Siniard, A. L., Wolfe, A. J., Curtis, D. R., Huentelman, M. J., & Carroll, C. C. (2018) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00014.2018 · Cited by 77
Exercise prescription for the older population: The interactions between physical activity, sedentary time, and adequate nutrition in maintaining musculoskeletal health
Shad, B. J., Wallis, G. A., van Loon, L. J. C., & Thompson, J. L. (2016) · Maturitas · doi:10.1016/j.maturitas.2016.05.016 · Cited by 78
Greater loss of mitochondrial function with ageing is associated with earlier onset of sarcopenia in C. elegans
Gaffney, C. J., Pollard, A. K., Barratt, T. F., Constantin‐Teodosiu, D., Greenhaff, P. L., & Szewczyk, N. J. (2018) · Aging · doi:10.18632/aging.101654 · Cited by 75
A coding and non-coding transcriptomic perspective on the genomics of human metabolic disease
Timmons, J. A., Atherton, P. J., Larsson, O. S., Sood, S., Blokhin, I. O., Brogan, R. J., Volmar, C., Josse, A. R., Slentz, C. A., Wahlestedt, C., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky570 · Cited by 70
Self-citation
Exercise and the regulation of skeletal muscle hypertrophy
McGlory, C., & Phillips, S. M. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.06.018 · Cited by 69
Sarcopenia: What Is the Origin of This Aging-Induced Disorder?
Gustafsson, T. P., & Ulfhake, B. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.688526 · Cited by 78
Self-citation
Gene expression profile of muscle adaptation to high-intensity intermittent exercise training in young men
Miyamoto‐Mikami, E., Tsuji, K., Horii, N., Hasegawa, N., Fujie, S. J., Homma, T., Uchida, M., Hamaoka, T., Kanehisa, H., Tabata, I., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-35115-x · Cited by 66
Mitochondrial Adaptations in Elderly and Young Men Skeletal Muscle Following 2 Weeks of Bed Rest and Rehabilitation
Buso, A., Comelli, M., Picco, R., Isola, M., Magnesa, B., Pišot, R., Rittweger, J., Salvadego, D., Šimunič, B., Grassi, B., et al. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00474 · Cited by 67
The HERITAGE family study: a review of the effects of exercise training on cardiometabolic health, with insights into molecular transducers
SARZYNSKI, M. A., RICE, T. K., DESPRÉS, J.-P., PÉRUSSE, L., TREMBLAY, A., STANFORTH, P. R., TCHERNOF, A., BARBER, J. L., FALCIANI, F., CLISH, C., et al. (2022) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002859 · Cited by 62
Self-citation
Transient transcriptional events in human skeletal muscle at the outset of concentric resistance exercise training
Murton, A. J., Billeter, R., Stephens, F. B., Etages, S. G. D., Graber, F., Hill, R. J. W., Marimuthu, K., & Greenhaff, P. L. (2013) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00426.2013 · Cited by 63
Protein Ingestion Increases Myofibrillar Protein Synthesis after Concurrent Exercise
CAMERA, D. M., West, D. W. D., Phillips, S. M., Rerecich, T., Stellingwerff, T., Hawley, J. A., & Coffey, V. G. (2014) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000390 · Cited by 66
State of Knowledge on Molecular Adaptations to Exercise in Humans: Historical Perspectives and Future Directions
Lavin, K. M., Coen, P. M., Baptista, L. C. P., Bell, M. B., Drummer, D. J., Harper, S. A., Lixandrão, M. E., McAdam, J. S., O’Bryan, S. M., Ramos, S. V., et al. (2022) · Comprehensive physiology · doi:10.1002/cphy.c200033 · Cited by 78
Arterial Oxygen Content Is Precisely Maintained by Graded Erythrocytotic Responses in Settings of High/Normal Serum Iron Levels, and Predicts Exercise Capacity: An Observational Study of Hypoxaemic Patients with Pulmonary Arteriovenous Malformations
Santhirapala, V., Williams, L. C., Tighe, H. C., Jackson, J. E., & Shovlin, C. L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090777 · Cited by 59
Nutritional strategies to support concurrent training
Pérez‐Schindler, J., Hamilton, D. L., Moore, D. R., Baar, K., & Philp, A. (2014) · European Journal of Sport Science · doi:10.1080/17461391.2014.950345 · Cited by 63
Mammalian Target of Rapamycin (mTOR) Signaling at the Crossroad of Muscle Fiber Fate in Sarcopenia
Sirago, G., Picca, A., Calvani, R., Coelho‐Júnior, H. J., & Marzetti, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213823 · Cited by 61
Optimized dietary strategies to protect skeletal muscle mass during periods of unavoidable energy deficit
Pasiakos, S. M., Margolis, L. M., & Orr, J. S. (2014) · The FASEB Journal · doi:10.1096/fj.14-266890 · Cited by 56
Resistance Exercise, Aging, Disuse, and Muscle Protein Metabolism
McKendry, J., Stokes, T., Mcleod, J. C., & Phillips, S. M. (2021) · Comprehensive physiology · doi:10.1002/cphy.c200029 · Cited by 78
Molecular Transducers of Human Skeletal Muscle Remodeling under Different Loading States
Stokes, T., Timmons, J. A., Crossland, H., Tripp, T. R., Murphy, K., McGlory, C., Mitchell, C. J., Oikawa, S. Y., Morton, R. W., Phillips, B. E., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107980 · Cited by 52
Self-citation
Resistance training in young men induces muscle transcriptome-wide changes associated with muscle structure and metabolism refining the response to exercise-induced stress
Damas, F., Ugrinowitsch, C., Libardi, C. A., Jannig, P. R., Hector, A. J., McGlory, C., Lixandrão, M. E., VECHIN, F. C., Montenegro, H., Tricoli, V., et al. (2018) · European Journal of Applied Physiology · doi:10.1007/s00421-018-3984-y · Cited by 51
A molecular signature defining exercise adaptation with ageing and in vivo partial reprogramming in skeletal muscle
Jones, R. G., Dimet‐Wiley, A., Haghani, A., da Silva, F. M., Brightwell, C. R., Lim, S., Khadgi, S., Wen, Y., Dungan, C. M., Brooke, R. T., et al. (2022) · The Journal of Physiology · doi:10.1113/jp283836 · Cited by 48
Integrative pathway analysis of a genome-wide association study of V o 2maxresponse to exercise training
Ghosh, S., Vivar, J. C., Sarzynski, M. A., Sung, Y. J., Timmons, J. A., Bouchard, C., & Rankinen, T. (2013) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01487.2012 · Cited by 51
Self-citation
Evaluating endoplasmic reticulum stress and unfolded protein response through the lens of ecology and evolution
Yap, K. N., Yamada, K. Y. H., Zikeli, S., Kiaris, H., & Hood, W. R. (2020) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12667 · Cited by 47
Angiogenesis-related ultrastructural changes to capillaries in human skeletal muscle in response to endurance exercise
Baum, O., Gübeli, J., Frese, S., Torchetti, E., Malik, C., Odriozola, A., Graber, F., Hoppeler, H. H., & Tschanz, S. A. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00594.2015 · Cited by 47
It's not just about protein turnover: the role of ribosomal biogenesis and satellite cells in the regulation of skeletal muscle hypertrophy
Brook, M. S., Wilkinson, D. J., Smith, K., & Atherton, P. J. (2019) · European Journal of Sport Science · doi:10.1080/17461391.2019.1569726 · Cited by 47
Self-citation
Recurrent training rejuvenates and enhances transcriptome and methylome responses in young and older human muscle
Blocquiaux, S., Ramaekers, M., Thienen, R. V., Nielens, H., Delecluse, C., Bock, K. D., & Thomis, M. A. (2021) · JCSM Rapid Communications · doi:10.1002/rco2.52 · Cited by 39
Response Heterogeneity With Exercise Training and Physical Activity Interventions Among Persons With Multiple Sclerosis
Baird, J. F., & Motl, R. W. (2018) · Neurorehabilitation and neural repair · doi:10.1177/1545968318818904 · Cited by 44
Longevity‐related molecular pathways are subject to midlife “switch” in humans
Timmons, J. A., Volmar, C., Crossland, H., Phillips, B. E., Sood, S., Janczura, K. J., Törmäkangas, T., Kujala, U. M., Kraus, W. E., Atherton, P. J., et al. (2019) · Aging Cell · doi:10.1111/acel.12970 · Cited by 41
Self-citation
Transcriptomic meta‐analysis of disuse muscle atrophy vs. resistance exercise‐induced hypertrophy in young and older humans
Deane, C. S., Willis, C. R. G., Phillips, B. E., Atherton, P. J., Harries, L. W., Ames, R. M., Szewczyk, N. J., & Etheridge, T. (2021) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12706 · Cited by 42
Self-citation
Age-Associated Differences in Recovery from Exercise-Induced Muscle Damage
Li, D. C. W., Rudloff, S., Langer, H. T., Norman, K., & Herpich, C. (2024) · Cells · doi:10.3390/cells13030255 · Cited by 45
Identification of a KLF5-dependent program and drug development for skeletal muscle atrophy
Liu, L., Koike, H., Ono, T., Hayashi, S., Kudo, F., Kaneda, A., Kagechika, H., Manabe, I., Nakashima, T., & Oishi, Y. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2102895118 · Cited by 42
Short‐term pre‐operative high‐intensity interval training does not improve fitness of colorectal cancer patients
Boereboom, C., Blackwell, J., Williams, J. P., Phillips, B. E., & Lund, J. N. (2019) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/sms.13460 · Cited by 45
Self-citation
Changes in Gene Expression in Responders and Nonresponders to a Low-Intensity Walking Intervention
Osler, M. E., Fritz, T., Caidahl, K., Krook, A., Zierath, J. R., & Wallberg‐Henriksson, H. (2015) · Diabetes Care · doi:10.2337/dc14-2606 · Cited by 39
Advances in Exercise, Fitness, and Performance Genomics in 2013
Wolfarth, B., Rankinen, T., Hagberg, J. M., Loos, R. J. F., Përusse, L., Roth, S. M., Sarzynski, M. A., & Bouchard, C. (2014) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000300 · Cited by 39
Self-citation
Muscle Proteomic and Transcriptomic Profiling of Healthy Aging and Metabolic Syndrome in Men
Gueugneau, M., Coudy‐Gandilhon, C., Chambon, C., Verney, J., Taillandier, D., Combaret, L., Polge, C., Walrand, S., Roche, F., Barthélemy, J., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084205 · Cited by 40
The link between Mitochondria and Sarcopenia
Kamarulzaman, N. T., & Makpol, S. (2025) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-024-01062-7 · Cited by 33
Aerobic exercise augments muscle transcriptome profile of resistance exercise
Lundberg, T. R., Fernandez‐Gonzalo, R., Tesch, P. A., Rullman, E., & Gustafsson, T. P. (2016) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00035.2016 · Cited by 32
Self-citation
The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth
Edman, S., Jones, R. G., Jannig, P. R., Fernandez‐Gonzalo, R., Norrbom, J., Thomas, N. T., Khadgi, S., Koopmans, P. J., da Silva, F. M., Chambers, T. L., et al. (2024) · EMBO Reports · doi:10.1038/s44319-024-00299-z · Cited by 44
Exercise and Regulation of Protein Metabolism
Atherton, P. J., Phillips, B. E., & Wilkinson, D. J. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.06.015 · Cited by 36
Self-citation
Chronic aryl hydrocarbon receptor activity phenocopies smoking‐induced skeletal muscle impairment
Thome, T., Míguez, K., Willms, A. J., Burke, S., Chandran, V., de Souza, A. R., Fitzgerald, L. F., Baglole, C. J., Anagnostou, M., Bourbeau, J., et al. (2021) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12826 · Cited by 32
The metabolic and temporal basis of muscle hypertrophy in response to resistance exercise
Brook, M. S., Wilkinson, D. J., Smith, K., & Atherton, P. J. (2015) · European Journal of Sport Science · doi:10.1080/17461391.2015.1073362 · Cited by 36
Self-citation
Exercise and Gene Expression
Hargreaves, M. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.07.006 · Cited by 32
The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks
Clarke, K., Ricciardi, S., Pearson, T., Bharudin, I., Davidsen, P. K., Bonomo, M., Brina, D., Scagliola, A., Simpson, D. M., Beynon, R. J., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.10.040 · Cited by 29
Self-citation
Gut Microbiota, Microbial Metabolites and Human Physical Performance
Lensu, S., & Pekkala, S. (2021) · Metabolites · doi:10.3390/metabo11110716 · Cited by 32
Short‐term aerobic conditioning prior to resistance training augments muscle hypertrophy and satellite cell content in healthy young men and women
Thomas, A. C. Q., Brown, A., Hatt, A. A., Manta, K., Costa‐Parke, A., Kamal, M. J., Joanisse, S., McGlory, C., Phillips, S. M., Kumbhare, D. A., et al. (2022) · The FASEB Journal · doi:10.1096/fj.202200398rr · Cited by 29
Parathyroid hormone-related peptide.
Kaiser, S. M., & Goltzman, D. (1993) · PubMed · Cited by 30
Transcriptomics for Clinical and Experimental Biology Research: Hang on a Seq
Stokes, T., Cen, H. H., Kapranov, P., Gallagher, I. J., Pitsillides, A. A., Volmar, C., Kraus, W. E., Johnson, J. D., Phillips, S. M., Wahlestedt, C., et al. (2023) · Advanced Genetics · doi:10.1002/ggn2.202200024 · Cited by 28
Self-citation
Resistance Training Improves Hyperglycemia and Dyslipidemia, Highly Prevalent Among Nonelderly, Nondiabetic, Chronically Disabled Stroke Patients
Zou, J., Wang, Z., Qu, Q., & Wang, L. (2015) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/j.apmr.2015.03.008 · Cited by 29
Altered mitochondrial microenvironment at the spotlight of musculoskeletal aging and Alzheimer’s disease
Giannos, P., Prokopidis, K., Raleigh, S. M., Kelaiditi, E., & Hill, M. W. (2022) · Scientific Reports · doi:10.1038/s41598-022-15578-9 · Cited by 28
Higher resistance training volume offsets muscle hypertrophy nonresponsiveness in older individuals
Lixandrão, M. E., Bamman, M. M., VECHIN, F. C., Conceição, M. S., Telles, G. D., Longobardi, I., Damas, F., Lavin, K. M., Drummer, D. J., McAdam, J. S., et al. (2024) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00670.2023 · Cited by 27
Proteomic features of skeletal muscle adaptation to resistance exercise training as a function of age
Deane, C. S., Phillips, B. E., Willis, C. R. G., Wilkinson, D. J., Smith, K., Higashitani, N., Williams, J. P., Szewczyk, N. J., Atherton, P. J., Higashitani, A., et al. (2022) · GeroScience · doi:10.1007/s11357-022-00658-5 · Cited by 29
Self-citation
Omics/systems biology and cancer cachexia
Gallagher, I. J., Jacobi, C., Tardif, N., Rooyackers, O., & Fearon, K. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.12.022 · Cited by 28
LINCing Nuclear Mechanobiology With Skeletal Muscle Mass and Function
van Ingen, M. J. A., & Kirby, T. J. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.690577 · Cited by 26
From molecular to physical function: The aging trajectory
Janssen, T., Lowisz, C. V., & Phillips, S. M. (2024) · Current Research in Physiology · doi:10.1016/j.crphys.2024.100138 · Cited by 31
Mitochondrial sulfide promotes life span and health span through distinct mechanisms in developing versus adult treated Caenorhabditis elegans
Vintila, A. R., Slade, L., Cooke, M., Willis, C. R. G., Torregrossa, R., Rahman, M., Anupom, T., Vanapalli, S. A., Gaffney, C. J., Gharahdaghi, N., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2216141120 · Cited by 25

Authors: Phillips, B. E., Williams, J. P., Gustafsson, T., Bouchard, C., Rankinen, T., Knudsen, S., Smith, K., Timmons, J. A., & Atherton, P. J.
Affiliations: Royal Derby Hospital (GB)
Karolinska Institutet (SE)
Pennington Biomedical Research Center (US)
Medical Prognosis Institute (Denmark) (DK)
Loughborough University (GB)
Corresponding author: Timmons, James A.
ORCID: Phillips, Bethan E.
Williams, John P.
Gustafsson, Thomas
Bouchard, Claude
Knudsen, Steen
Smith, Kenneth
Timmons, James A.
Atherton, Philip J.
Venue: PLoS Genetics
Publisher: Public Library of Science (PLoS)
Published: 2013-03-21
Volume: 9
Issue: 3
Pages: e1003389
ISSN: 1553-7390 (ISSN-L)
1553-7404
DOI: 10.1371/journal.pgen.1003389
PMC: PMC3605101
OpenAlex: W2094388228
Cited by: 199
References: 90
Citations by year: 2026: 6 · 2025: 6 · 2024: 14 · 2023: 13 · 2022: 18 · 2021: 22 · 2020: 13 · 2019: 17 · 2018: 17 · 2017: 9 · 2016: 16 · 2015: 23 · 2014: 18 · 2013: 6
FWCI: 9.41
Type: journal article
Language: en
Update notices: correction (2013-04-25)
correction (2013-04-03)
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS Genetics (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Nottingham ePrints (University of Nottingham) (submittedVersion)
Figshare (submittedVersion, cc-by)
Funders: University of Stirling
National Institutes of Health (HL- 47317, HL- 47327, HL- 47323)
Directorate for Biological Sciences
Medical Research Council (MR/K00414X/1)
Biotechnology and Biological Sciences Research Council (BB/X5106971, BB/C516779/1)
National Heart, Lung, and Blood Institute (R01HL047327, HL 47321, HL 45670, HL47323, R01HL047317, HL 47327, R01HL047323, HL47317, R01HL045670, R01HL047321)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
Keywords: muscle aging, resistance training, endurance training, sarcopenia, mTOR signaling, rapamycin, muscle hypertrophy, lean body mass, all-trans retinoic acid, aryl hydrocarbon receptor signaling, age-related gene expression, post-transcriptional regulation, ribosomal genes, gene regulatory networks
MeSH terms: Adaptation, Physiological, Adolescent, Adult, Aged, Aging, Female, Humans, Male, Middle Aged, Signal Transduction, Exercise, Down-Regulation, Muscle, Skeletal, Gene Expression Profiling, Gene Regulatory Networks, Ribosome Subunits, TOR Serine-Threonine Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Molecular Networks of Human Muscle Adaptation to Exercise and Age

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks