Regular engagement in resistance exercise training elicits many health benefits including improvement to muscular strength, hypertrophy and insulin sensitivity, though the underpinning molecular mechanisms are poorly understood. The purpose of this study was to determine the influence 8 weeks of resistance exercise training has on leukocyte genome-wide DNA methylation and gene expression in healthy young men.
Eight young (21.1 ± 2.2 years) men completed one repetition maximum (1RM) testing before completing 8 weeks of supervised, thrice-weekly resistance exercise training comprising three sets of 8–12 repetitions with a load equivalent to 80 % of 1RM. Blood samples were collected at rest before and after the 8-week training intervention. Genome-wide DNA methylation and gene expression were assessed on isolated leukocyte DNA and RNA using the 450K BeadChip and HumanHT-12 v4 Expression BeadChip (Illumina), respectively.
Resistance exercise training significantly improved upper and lower body strength concurrently with diverse genome-wide DNA methylation and gene expression changes (p ≤ 0. 01). DNA methylation changes occurred at multiple regions throughout the genome in context with genes and CpG islands, and in genes relating to axon guidance, diabetes and immune pathways. There were multiple genes with increased expression that were enriched for RNA processing and developmental proteins. Growth factor genes—GHRH and FGF1—showed differential methylation and mRNA expression changes after resistance training.
Our findings indicate that resistance exercise training improves muscular strength and is associated with reprogramming of the leukocyte DNA methylome and transcriptome.
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Analysis of variance
- χ 2 :
Cytosine neighbouring a guanine dinucleotide
Database for Annotation, Visualization and Integrated Discovery
Fibroblast growth factor 1
Growth hormone-releasing hormone
International Physical Activity Questionnaire
Metabolic equivalent of task
Nuclear factor of kappa light polypeptide gene enhancer in B-cells
One repetition maximum
Resistance exercise training
Tet methylcytosine dioxygenase
Anderson OS, Sant KE, Dolinoy DC (2012) Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J Nutr Biochem 23(8):853–859
Bemben DA, Bemben MG (2011) Dose-response effect of 40 weeks of resistance training on bone mineral density in older adults. Osteoporos Int 22(1):179–186
Beniamini Y, Rubenstein JJ, Zaichkowsky LD, Crim MC (1997) Effects of high-intensity strength training on quality-of-life parameters in cardiac rehabilitation patients. Am J Cardiol 80(7):841–846
Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16(1):6–21
Booth FW, Roberts CK, Laye MJ (2012) Lack of exercise is a major cause of chronic diseases. Compr Physiol 2(2):1143–1211
Braith RW, Stewart KJ (2006) Resistance exercise training: its role in the prevention of cardiovascular disease. Circulation 113(22):2642–2650
Buttner P, Mosig S, Lechtermann A, Funke H, Mooren FC (2007) Exercise affects the gene expression profiles of human white blood cells. J Appl Physiol (1985) 102(1):26–36
Carlson LA, Tighe SW, Kenefick RW et al (2011) Changes in transcriptional output of human peripheral blood mononuclear cells following resistance exercise. Eur J Appl Physiol 111(12):2919–2929
Cedar H, Bergman Y (2012) Programming of DNA methylation patterns. Annu Rev Biochem 81:97–117
Connolly PH, Caiozzo VJ, Zaldivar F et al (2004) Effects of exercise on gene expression in human peripheral blood mononuclear cells. J Appl Physiol (1985) 97(4):1461–1469
Cornelissen VA, Smart NA (2013) Exercise training for blood pressure: a systematic review and meta-analysis. J Am Heart Assoc 2(1):e004473
Cornelissen VA, Fagard RH, Coeckelberghs E, Vanhees L (2011) Impact of resistance training on blood pressure and other cardiovascular risk factors: a meta-analysis of randomized, controlled trials. Hypertension 58(5):950–958
da Huang W, Sherman BT, Lempicki RA (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37(1):1–13
Denham J, Marques FZ, O’Brien BJ, Charchar FJ (2014) Exercise: putting action into our epigenome. Sports Med 44(2):189–209
Denham J, O’Brien BJ, Harvey JT, Charchar FJ (2015a) Genome-wide sperm DNA methylation changes after 3 months of exercise training in humans. Epigenomics 7:717–731
Denham J, O’Brien BJ, Marques FZ, Charchar FJ (2015b) Changes in the leukocyte methylome and its effect on cardiovascular-related genes after exercise. J Appl Physiol (1985) 118(4):475–488
Dunstan DW, Daly RM, Owen N et al (2002) High-intensity resistance training improves glycemic control in older patients with type 2 diabetes. Diabetes Care 25(10):1729–1736
Gordon BA, Benson AC, Bird SR, Fraser SF (2009) Resistance training improves metabolic health in type 2 diabetes: a systematic review. Diabetes Res Clin Pract 83(2):157–175
Grayson DR, Guidotti A (2013) The dynamics of DNA methylation in schizophrenia and related psychiatric disorders. Neuropsychopharmacology 38(1):138–166
He YF, Li BZ, Li Z et al (2011) Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333(6047):1303–1307
Heyn H, Esteller M (2012) DNA methylation profiling in the clinic: applications and challenges. Nat Rev Genet 13(10):679–692
Hinton PS, Nigh P, Thyfault J (2015) Effectiveness of resistance training or jumping-exercise to increase bone mineral density in men with low bone mass: a 12-month randomized, clinical trial. Bone 79:203–212
Hulmi JJ, Kovanen V, Selanne H et al (2009) Acute and long-term effects of resistance exercise with or without protein ingestion on muscle hypertrophy and gene expression. Amino Acids 37(2):297–308
Inoue A, Zhang Y (2011) Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation embryos. Science 334(6053):194
Katula JA, Rejeski WJ, Marsh AP (2008) Enhancing quality of life in older adults: a comparison of muscular strength and power training. Health Qual Life Outcomes 6:45
Kelley GA, Kelley KS (2009) Impact of progressive resistance training on lipids and lipoproteins in adults: a meta-analysis of randomized controlled trials. Prev Med 48(1):9–19
Lindholm ME, Marabita F, Gomez-Cabrero D et al (2014) An integrative analysis reveals coordinated reprogramming of the epigenome and the transcriptome in human skeletal muscle after training. Epigenetics 9(12):1557–1569
Liu D, Sartor MA, Nader GA et al (2010) Skeletal muscle gene expression in response to resistance exercise: sex specific regulation. BMC Genom 11:659
McFarlin BK, Flynn MG, Campbell WW, Stewart LK, Timmerman KL (2004) TLR4 is lower in resistance-trained older women and related to inflammatory cytokines. Med Sci Sports Exerc 36(11):1876–1883
Nilsson EE, Skinner MK (2015) Environmentally induced epigenetic transgenerational inheritance of disease susceptibility. Transl Res 165(1):12–17
Nitert MD, Dayeh T, Volkov P et al (2012) Impact of an exercise intervention on DNA methylation in skeletal muscle from first-degree relatives of patients with type 2 diabetes. Diabetes 61(12):3322–3332
Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99(3):247–257
Pedersen BK, Saltin B (2006) Evidence for prescribing exercise as therapy in chronic disease. Scand J Med Sci Sports 16(Suppl 1):3–63
Phillips MD, Patrizi RM, Cheek DJ et al (2012) Resistance training reduces subclinical inflammation in obese, postmenopausal women. Med Sci Sports Exerc 44(11):2099–2110
Pillon NJ, Bilan PJ, Fink LN, Klip A (2013) Cross-talk between skeletal muscle and immune cells: muscle-derived mediators and metabolic implications. Am J Physiol Endocrinol Metab 304(5):E453–E465
Radom-Aizik S, Zaldivar F Jr, Leu SY, Galassetti P, Cooper DM (2008) Effects of 30 min of aerobic exercise on gene expression in human neutrophils. J Appl Physiol (1985) 104(1):236–243
Raue U, Trappe TA, Estrem ST et al (2012) Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults. J Appl Physiol (1985) 112(10):1625–1636
Ronn T, Volkov P, Davegardh C et al (2013) A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet 9(6):e1003572
Rowlands DS, Page RA, Sukala WR et al (2014) Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity. Physiol Genomics 46(20):747–765
Schermelleh L, Haemmer A, Spada F et al (2007) Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation. Nucleic Acids Res 35(13):4301–4312
Schuler G, Adams V, Goto Y (2013) Role of exercise in the prevention of cardiovascular disease: results, mechanisms, and new perspectives. Eur Heart J 34(24):1790–1799
Singh NA, Clements KM, Fiatarone MA (1997) A randomized controlled trial of progressive resistance training in depressed elders. J Gerontol A Biol Sci Med Sci 52(1):M27–M35
Stepto NK, Coffey VG, Carey AL et al (2009) Global gene expression in skeletal muscle from well-trained strength and endurance athletes. Med Sci Sports Exerc 41(3):546–565
Strasser B, Arvandi M, Siebert U (2012) Resistance training, visceral obesity and inflammatory response: a review of the evidence. Obes Rev 13(7):578–591
Tahiliani M, Koh KP, Shen Y et al (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324(5929):930–935
Thompson D, Markovitch D, Betts JA et al (2010) Time course of changes in inflammatory markers during a 6-mo exercise intervention in sedentary middle-aged men: a randomized-controlled trial. J Appl Physiol (1985) 108(4):769–779
Tidball JG (2005) Inflammatory processes in muscle injury and repair. Am J Physiol Regul Integr Comp Physiol 288(2):R345–R353
Tidball JG, Villalta SA (2010) Regulatory interactions between muscle and the immune system during muscle regeneration. Am J Physiol Regul Integr Comp Physiol 298(5):R1173–R1187
Tresierras MA, Balady GJ (2009) Resistance training in the treatment of diabetes and obesity: mechanisms and outcomes. J Cardiopulm Rehabil Prev 29(2):67–75
Volkmar M, Dedeurwaerder S, Cunha DA et al (2012) DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients. EMBO J 31(6):1405–1426
Westcott WL (2012) Resistance training is medicine: effects of strength training on health. Curr Sports Med Rep 11(4):209–216
Zaina S, Heyn H, Carmona FJ et al (2014) DNA methylation map of human atherosclerosis. Circ Cardiovasc Genet 7(5):692–700
We thank the Australian Genome Research Facility for the help with the arrays.
Conflict of interest
This work was supported by the Federation University Australia ‘Self-sustaining Regions Research Innovation Initiative’ and the Australian Government Collaborative Research Network (CRN). This work was also supported by a Federation University Australia Faculty of Health Seeding Grant obtained by B.J.O and F.Z.M. F.Z.M is supported by the National Health and Medical Research Council (APP1052659) and National Heart Foundation (PF12M6785) co-shared Early Career Fellowships. F.J.C is supported by the Lew Carty Charitable Fund and National Health and Medical Research Council of Australia.
Communicated by William J. Kraemer.
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Denham, J., Marques, F.Z., Bruns, E.L. et al. Epigenetic changes in leukocytes after 8 weeks of resistance exercise training. Eur J Appl Physiol 116, 1245–1253 (2016). https://doi.org/10.1007/s00421-016-3382-2
- Strength training
- mRNA expression
- DNA methylation