Exercise: Putting action into our epigenome

Sports Medicine

Volumn 44, Issue 2, 2014, Pages 189-209

  Denham, Joshua ^a   Marques, Francine Z ^a   O'Brien, Brendan J ^a   Charchar, Fadi J ^a  

^a UNIVERSITY OF BALLARAT   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

MICRORNA;

CHRONIC DISEASE; EPIGENETICS; EXERCISE; GENE EXPRESSION; GENETIC PREDISPOSITION; GENETICS; HUMAN; HUMAN DEVELOPMENT; PHENOTYPE; PHYSIOLOGY; REVIEW;

CHRONIC DISEASE; EPIGENOMICS; EXERCISE; GENE EXPRESSION; GENETIC PREDISPOSITION TO DISEASE; HUMAN DEVELOPMENT; HUMANS; MICRORNAS; PHENOTYPE;

EID: 84894147944     PISSN: 01121642     EISSN: 11792035     Source Type: Journal    
DOI: 10.1007/s40279-013-0114-1     Document Type: Review

References (205)

1. de la Chapelle A. Genetic predisposition to human disease: allele-specific expression and low-penetrance regulatory loci. Oncogene. 2009;28:3345-8.
2. Diaz-Gallo LM, Palomino-Morales RJ, Gomez-Garcia M, et al. STAT4 gene influences genetic predisposition to ulcerative colitis but not Crohn's disease in the Spanish population: a replication study. Hum Immunol. 2010;71:515-9.
3. Ingles J, Yeates L, Hunt L, et al. Health status of cardiac genetic disease patients and their at-risk relatives. Int J Cardiol. 2013;165:448-53.
4. Charchar FJ, Bloomer LD, Barnes TA, et al. Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome. Lancet. 2012;379:915-22.
5. Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21:381-95.
6. Varley KE, Gertz J, Bowling KM, et al. Dynamic DNA methylation across diverse human cell lines and tissues. Genome Res. 2013;23:555-67.
7. Wang X, Falkner B, Zhu H, et al. A genome-wide methylation study on essential hypertension in young African American males. PLoS One. 2013;8:e53938.
8. Bartlett TE, Zaikin A, Olhede SC, et al. Corruption of the intra-gene DNA methylation architecture is a hallmark of cancer. PLoS One. 2013;8:e68285.
9. Heyn H, Esteller M. DNA methylation profiling in the clinic: applications and challenges. Nat Rev Genet. 2012;13:679-92.
10. van Empel VP, De Windt LJ, da Costa Martins PA. Circulating miRNAs: reflecting or affecting cardiovascular disease? Curr Hypertens Rep. 2012;14:498-509.
11. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12:861-74.
12. Na HK, Oliynyk S. Effects of physical activity on cancer prevention. Ann N Y Acad Sci. 2011;1229:176-83.
13. Jenkins NT, Martin JS, Laughlin MH, et al. Exercise-induced signals for vascular endothelial adaptations: implications for cardiovascular disease. Curr Cardiovasc Risk Rep. 2012;6:331-46.
14. Warburton DE, Nicol CW, Bredin SS. Health benefits of physical activity: the evidence. CMAJ. 2006;174:801-9.
15. Fraga MF, Ballestar E, Paz MF, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA. 2005;102:10604-9.
16. Waterland RA, Michels KB. Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr. 2007;27:363-88.
17. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128:693-705.
18. Ren H, Collins V, Clarke SJ, et al. Epigenetic changes in response to tai chi practice: a pilot investigation of DNA methylation marks. Evid Based Complement Alternat Med. 2012;2012:841810.
19. Barres R, Yan J, Egan B, et al. Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metabolism. 2012;15:405-11.
20. McGee SL, Fairlie E, Garnham AP, et al. Exercise-induced histone modifications in human skeletal muscle. J Physiol. 2009;587:5951-8.
21. Chandramohan Y, Droste SK, Arthur JS, et al. The forced swimming-induced behavioural immobility response involves histone H3 phospho-acetylation and c-Fos induction in dentate gyrus granule neurons via activation of the N-methyl-d-aspartate/extracellular signal-regulated kinase/mitogen- and stress-activated kinase signalling pathway. Eur J Neurosci. 2008;27:2701-13.
22. Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003;33(Suppl):245-54.
23. Fazzari MJ, Greally JM. Introduction to epigenomics and epigenome-wide analysis. Methods Mol Biol. 2010;620:243-65.
24. Bernardo BC, Charchar FJ, Lin RC, et al. A microRNA guide for clinicians and basic scientists: background and experimental techniques. Heart Lung Circ. 2012;21:131-42.
25. Eads CA, Danenberg KD, Kawakami K, et al. MethyLight: a high-throughput assay to measure DNA methylation. Nucleic Acids Res. 2000;28:E32.
26. Karimi M, Johansson S, Stach D, et al. LUMA (LUminometric Methylation Assay) - a high throughput method to the analysis of genomic DNA methylation. Exp Cell Res. 2006;312:1989-95.
27. Irizarry RA, Ladd-Acosta C, Carvalho B, et al. Comprehensive high-throughput arrays for relative methylation (CHARM). Genome Res. 2008;18:780-90.
28. de Ruijter AJ, van Gennip AH, Caron HN, et al. Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J. 2003;370:737-49.
29. Jirtle RL, Skinner MK. Environmental epigenomics and disease susceptibility. Nat Rev Genet. 2007;8:253-62.
30. Li Y, Zhu J, Tian G, et al. The DNA methylome of human peripheral blood mononuclear cells. PLoS Biol. 2010;8:e1000533.
31. Deaton AM, Bird A. CpG islands and the regulation of transcription. Genes Dev. 2011;25:1010-22.
32. Han H, Cortez CC, Yang X, et al. DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoter. Hum Mol Genet. 2011;20:4299-310.
33. Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012;13:484-92.
34. Defossez PA, Stancheva I. Biological functions of methyl-CpG-binding proteins. Prog Mol Biol Transl Sci. 2011;101:377-98.
35. Klose RJ, Bird AP. Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci. 2006;31:89-97.
36. Fang F, Hodges E, Molaro A, et al. Genomic landscape of human allele-specific DNA methylation. Proc Natl Acad Sci USA. 2012;109:7332-7.
37. Wutz A. Gene silencing in X-chromosome inactivation: advances in understanding facultative heterochromatin formation. Nat Rev Genet. 2011;12:542-53.
38. Mermoud JE, Popova B, Peters AH, et al. Histone H3 lysine 9 methylation occurs rapidly at the onset of random X chromosome inactivation. Curr Biol. 2002;12:247-51.
39. Wolff EM, Byun HM, Han HF, et al. Hypomethylation of a LINE-1 promoter activates an alternate transcript of the MET oncogene in bladders with cancer. PLoS Genet. 2010;6:e1000917.
40. Sunami E, de Maat M, Vu A, et al. LINE-1 hypomethylation during primary colon cancer progression. PLoS One. 2011;6:e18884.
41. Pavicic W, Joensuu EI, Nieminen T, et al. LINE-1 hypomethylation in familial and sporadic cancer. J Mol Med (Berl). 2012;90:827-35.
42. Lopez-Serra P, Esteller M. DNA methylation-associated silencing of tumor-suppressor microRNAs in cancer. Oncogene. 2012;31:1609-22.
43. Kuratomi G, Iwamoto K, Bundo M, et al. Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins. Mol Psychiatry. 2008;13:429-41.
44. Poulsen P, Esteller M, Vaag A, et al. The epigenetic basis of twin discordance in age-related diseases. Pediatr Res. 2007;61:38R-42R.
45. Deaton AM, Webb S, Kerr AR, et al. Cell type-specific DNA methylation at intragenic CpG islands in the immune system. Genome Res. 2011;21:1074-86.
46. Denis H, Ndlovu MN, Fuks F. Regulation of mammalian DNA methyltransferases: a route to new mechanisms. EMBO Rep. 2011;12:647-56.
47. Karpf AR, Matsui S. Genetic disruption of cytosine DNA methyltransferase enzymes induces chromosomal instability in human cancer cells. Cancer Res. 2005;65:8635-9.
48. Okano M, Bell DW, Haber DA, et al. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999;99:247-57.
49. Suetake I, Shinozaki F, Miyagawa J, et al. DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction. J Biol Chem. 2004;279:27816-23.
50. Niculescu MD, Zeisel SH. Diet, methyl donors and DNA methylation: interactions between dietary folate, methionine and choline. J Nutr. 2002;132:2333S-5S.
51. Ito S, D'Alessio AC, Taranova OV, et al. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature. 2010;466:1129-33.
52. Wu SC, Zhang Y. Active DNA demethylation: many roads lead to Rome. Nat Rev Mol Cell Biol. 2010;11:607-20.
53. Franchini DM, Schmitz KM, Petersen-Mahrt SK. 5-methylcytosine DNA demethylation: more than losing a methyl group. Annu Rev Genet. 2012;46:419-41.
54. Da Sacco L, Masotti A. Recent insights and novel bioinformatics tools to understand the role of microRNAs binding to 5' untranslated region. Int J Mol Sci. 2012;14:480-95.
55. Vasudevan S. Posttranscriptional upregulation by microRNAs. Wiley Interdiscip Rev RNA. 2012;3:311-30.
56. Kim YK, Kim VN. Processing of intronic microRNAs. EMBO J. 2007;26:775-83.
57. Rodriguez A, Griffiths-Jones S, Ashurst JL, et al. Identification of mammalian microRNA host genes and transcription units. Genome Res. 2004;14:1902-10.
58. Saini HK, Griffiths-Jones S, Enright AJ. Genomic analysis of human microRNA transcripts. Proc Natl Acad Sci USA. 2007;104:17719-24.
59. Yeom KH, Lee Y, Han J, et al. Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing. Nucl Acids Res. 2006;34:4622-9.
60. Zeng Y, Yi R, Cullen BR. Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. EMBO J. 2005;24:138-48.
61. Yi R, Qin Y, Macara IG, et al. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. 2003;17:3011-6.
62. Hutvagner G, McLachlan J, Pasquinelli AE, et al. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 2001;293:834-8.
63. Chendrimada TP, Gregory RI, Kumaraswamy E, et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature. 2005;436:740-4.
64. Winter J, Jung S, Keller S, et al. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009;11:228-34.
65. Okamura K, Ishizuka A, Siomi H, et al. Distinct roles for argonaute proteins in small RNA-directed RNA cleavage pathways. Genes Dev. 2004;18:1655-66.
66. Sood P, Krek A, Zavolan M, et al. Cell-type-specific signatures of microRNAs on target mRNA expression. Proc Natl Acad Sci USA. 2006;103:2746-51.
67. Gu S, Jin L, Zhang F, et al. Biological basis for restriction of microRNA targets to the 3' untranslated region in mammalian mRNAs. Nat Struct Mol Biol. 2009;16:144-50.
68. Lim LP, Lau NC, Garrett-Engele P, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433:769-73.
69. Betancur JG, Yoda M, Tomari Y. miRNA-like duplexes as RNAi triggers with improved specificity. Front Genet. 2012;3:127.
70. Marques MA, Combes M, Roussel B, et al. Impact of a mechanical massage on gene expression profile and lipid mobilization in female gluteofemoral adipose tissue. Obes Facts. 2011;4:121-9.
71. Nikitina EG, Urazova LN, Stegny VN. MicroRNAs and human cancer. Exp Oncol. 2012;34:2-8.
72. Fernandez-Valverde SL, Taft RJ, Mattick JS. MicroRNAs in beta-cell biology, insulin resistance, diabetes and its complications. Diabetes. 2011;60:1825-31.
73. Zampetaki A, Willeit P, Drozdov I, et al. Profiling of circulating microRNAs: from single biomarkers to re-wired networks. Cardiovasc Res. 2012;93:555-62.
74. McAlexander MA, Phillips MJ, Witwer KW. Comparison of methods for miRNA extraction from plasma and quantitative recovery of RNA from cerebrospinal fluid. Front Genet. 2013;4:83.
75. Pritchard CC, Cheng HH, Tewari M. MicroRNA profiling: approaches and considerations. Nat Rev Genet. 2012;13:358-69.
76. Cotman CW, Engesser-Cesar C. Exercise enhances and protects brain function. Exerc Sport Sci Rev. 2002;30:75-9.
77. Hillman CH, Erickson KI, Kramer AF. Be smart, exercise your heart: exercise effects on brain and cognition. Nat Rev Neurosci. 2008;9:58-65.
78. Podewils LJ, Guallar E, Kuller LH, et al. Physical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study. Am J Epidemiol. 2005;161:639-51.
79. Smith JA, Kohn TA, Chetty AK, et al. CaMK activation during exercise is required for histone hyperacetylation and MEF2A binding at the MEF2 site on the Glut4 gene. Am J Physiol Endocrinol Metab. 2008;295:E698-704.
80. Collins A, Hill LE, Chandramohan Y, et al. Exercise improves cognitive responses to psychological stress through enhancement of epigenetic mechanisms and gene expression in the dentate gyrus. PLoS One. 2009;4:e4330.
81. Abel JL, Rissman EF. Running-induced epigenetic and gene expression changes in the adolescent brain. Int J Dev Neurosci. 2013;31(6):382-90.
82. Elsner VR, Lovatel GA, Moyses F, et al. Exercise induces age-dependent changes on epigenetic parameters in rat hippocampus: a preliminary study. Exp Gerontol. 2012;48:136-9.
83. Mattson MP, Maudsley S, Martin B. BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci. 2004;27:589-94.
84. Gomez-Pinilla F, Ying Z, Roy RR, et al. Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J Neurophysiol. 2002;88:2187-95.
85. Gomez-Pinilla F, Zhuang Y, Feng J, et al. Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation. Eur J Neurosci. 2011;33:383-90.
86. Elsner VR, Lovatel GA, Bertoldi K, et al. Effect of different exercise protocols on histone acetyltransferases and histone deacetylases activities in rat hippocampus. Neuroscience. 2011;192:580-7.
87. Abel JL, Rissman EF. Running-induced epigenetic and gene expression changes in the adolescent brain. Int J Dev Neurosci. 2013;31:382-90.
88. McGee SL, Hargreaves M. Histone modifications and exercise adaptations. J Appl Physiol. 2011;110:258-63.
89. Mejat A, Ramond F, Bassel-Duby R, et al. Histone deacetylase 9 couples neuronal activity to muscle chromatin acetylation and gene expression. Nat Neurosci. 2005;8:313-21.
90. Cohen TJ, Barrientos T, Hartman ZC, et al. The deacetylase HDAC4 controls myocyte enhancing factor-2-dependent structural gene expression in response to neural activity. FASEB J. 2009;23:99-106.
91. Mukwevho E, Kohn TA, Lang D, et al. Caffeine induces hyperacetylation of histones at the MEF2 site on the Glut4 promoter and increases MEF2A binding to the site via a CaMK-dependent mechanism. Am J Physiol Endocrinol Metab. 2008;294:E582-8.
92. (2) uptake response to standardized exercise training programs. J Appl Physiol. 2011;110:1160-70.
93. Timmons JA, Knudsen S, Rankinen T, et al. Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. J Appl Physiol. 2010;108:1487-96.
94. Keller P, Vollaard NB, Gustafsson T, et al. A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype. J Appl Physiol. 2011;110:46-59.
95. Puthucheary Z, Skipworth JR, Rawal J, et al. The ACE gene and human performance: 12 years on. Sports Med. 2011;41:433-48.
96. Bouchard C. Genomic predictors of trainability. Exp Physiol. 2012;97:347-52.
97. Terruzzi I, Senesi P, Montesano A, et al. Genetic polymorphisms of the enzymes involved in DNA methylation and synthesis in elite athletes. Physiol Genomics. 2011;43:965-73.
98. Ehlert T, Simon P, Moser DA. Epigenetics in sports. Sports Med. 2013;43:93-110.
99. Raleigh SM. Epigenetic regulation of the ACE gene might be more relevant to endurance physiology than the I/D polymorphism. J Appl Physiol. 2012;112:1082-3.
100. Egan B, Carson BP, Garcia-Roves PM, et al. Exercise intensity-dependent regulation of peroxisome proliferator-activated receptor coactivator-1 mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle. J Physiol. 2010;588:1779-90.
101. Drummond MJ, McCarthy JJ, Fry CS, et al. Aging differentially affects human skeletal muscle microRNA expression at rest and after an anabolic stimulus of resistance exercise and essential amino acids. Am J Physiol Endocrinol Metab. 2008;295:E1333-40.
102. Russell AP, Lamon S, Boon H, et al. Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short term endurance training. J Physiol. 2013;591(Pt 18):4637-53.
103. Imamura T, Yamamoto S, Ohgane J, et al. Non-coding RNA directed DNA demethylation of Sphk1 CpG island. Biochem Biophys Res Commun. 2004;322:593-600.
104. Mohammad F, Pandey GK, Mondal T, et al. Long noncoding RNA-mediated maintenance of DNA methylation and transcriptional gene silencing. Development. 2012;139:2792-803.
105. Lee IM, Paffenbarger RS Jr. Associations of light, moderate, and vigorous intensity physical activity with longevity. The Harvard Alumni Health Study. Am J Epidemiol. 2000;151:293-9.
106. Monninkhof EM, Elias SG, Vlems FA, et al. Physical activity and breast cancer: a systematic review. Epidemiology. 2007;18:137-57.
107. Quadrilatero J, Hoffman-Goetz L. Physical activity and colon cancer. A systematic review of potential mechanisms. J Sports Med Phys Fitness. 2003;43:121-38.
108. Lee IM, Hsieh CC, Paffenbarger RS Jr. Exercise intensity and longevity in men. The Harvard Alumni Health Study. JAMA. 1995;273:1179-84.
109. Gibala MJ, Little JP, Macdonald MJ, et al. Physiological adaptations to low-volume, high-intensity interval training in health and disease. J Physiol. 2012;590:1077-84.
110. Paulsen G, Myklestad D, Raastad T. The influence of volume of exercise on early adaptations to strength training. J Strength Cond Res. 2003;17:115-20.
111. Ringholm S, Bienso RS, Kiilerich K, et al. Bed rest reduces metabolic protein content and abolishes exercise-induced mRNA responses in human skeletal muscle. Am J Physiol Endocrinol Metab. 2011;301:e649-58.
112. Alibegovic AC, Sonne MP, Hojbjerre L, et al. Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men. Am J Physiol Endocrinol Metab. 2010;299:e752-63.
113. Nitert MD, Dayeh T, Volkov P, et al. Impact of an exercise Intervention on DNA methylation in skeletal muscle from first-degree relatives of patients with type 2 diabetes. Diabetes. 2012;61:3322-32.
114. Ronn T, Volkov P, Davegardh C, et al. A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet. 2013;9:e1003572.
115. Zhang FF, Cardarelli R, Carroll J, et al. Physical activity and global genomic DNA methylation in a cancer-free population. Epigenetics. 2011;6:293-9.
116. Zhang FF, Santella RM, Wolff M, et al. White blood cell global methylation and IL-6 promoter methylation in association with diet and lifestyle risk factors in a cancer-free population. Epigenetics. 2012;7:606-14.
117. Maeda T, Oyama J, Higuchi Y, et al. The physical ability of Japanese female elderly with cerebrovascular disease correlates with the telomere length and subtelomeric methylation status in their peripheral blood leukocytes. Gerontology. 2011;57:137-43.
118. Nakajima K, Takeoka M, Mori M, et al. Exercise effects on methylation of ASC gene. Int J Sports Med. 2010;31:671-5.
119. Zeng H, Irwin ML, Lu L, et al. Physical activity and breast cancer survival: an epigenetic link through reduced methylation of a tumor suppressor gene L3MBTL1. Breast Cancer Res Treat. 2012;133:127-35.
120. Lott SA, Burghardt PR, Burghardt KJ, et al. The influence of metabolic syndrome, physical activity and genotype on catechol-O-methyl transferase promoter-region methylation in schizophrenia. Pharmacogenomics J. 2013;13:264-71.
121. Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868-74.
122. Marx J. Cancer research. Inflammation and cancer: the link grows stronger. Science. 2004;306:966-8.
123. Franks AL, Slansky JE. Multiple associations between a broad spectrum of autoimmune diseases, chronic inflammatory diseases and cancer. Anticancer Res. 2012;32:1119-36.
124. Cannizzo ES, Clement CC, Sahu R, et al. Oxidative stress, inflamm-aging and immunosenescence. J Proteomics. 2011;74:2313-23.
125. Gleeson M, Bishop NC, Stensel DJ, et al. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol. 2011;11:607-15.
126. Walsh NP, Gleeson M, Shephard RJ, et al. Position statement. Part one: Immune function and exercise. Exerc Immunol Rev. 2011;17:6-63.
127. Tomaszewski M, Charchar FJ, Przybycin M, et al. Strikingly low circulating CRP concentrations in ultramarathon runners independent of markers of adiposity: how low can you go? Arterioscler Thromb Vasc Biol. 2003;23:1640-4.
128. Heyn H, Li N, Ferreira HJ, et al. Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci USA. 2012;109:10522-7.
129. Gopalakrishnan S, Van Emburgh BO, Robertson KD. DNA methylation in development and human disease. Mutat Res. 2008;647:30-8.
130. Robertson KD. DNA methylation and human disease. Nat Rev Genet. 2005;6:597-610.
131. Blackburn EH. Structure and function of telomeres. Nature. 1991;350:569-73.
132. Oeseburg H, de Boer RA, van Gilst WH, et al. Telomere biology in healthy aging and disease. Pflugers Arch. 2010;459:259-68.
133. Cawthon RM, Smith KR, O'Brien E, et al. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet. 2003;361:393-5.
134. Denham J, Nelson CP, O'Brien BJ, et al. Longer leukocyte telomeres are associated with ultra-endurance exercise independent of cardiovascular risk factors. PLoS One. 2013;8:e69377.
135. Kaliman P, Parrizas M, Lalanza JF, et al. Neurophysiological and epigenetic effects of physical exercise on the aging process. Ageing Res Rev. 2011;10:475-86.
136. Sanchis-Gomar F, Garcia-Gimenez JL, Perez-Quilis C, et al. Physical exercise as an epigenetic modulator: Eustress, the "positive stress" as an effector of gene expression. J Strength Cond Res. 2012;26:3469-72.
137. Ntanasis-Stathopoulos J, Tzanninis JG, Philippou A, et al. Epigenetic regulation on gene expression induced by physical exercise. J Musculoskelet Neuronal Interact. 2013;13:133-46.
138. White AJ, Sandler DP, Bolick SC, et al. Recreational and household physical activity at different time points and DNA global methylation. Eur J Cancer. Epub 2013 Mar 6.
139. Luttropp K, Nordfors L, Ekstrom TJ, et al. Physical activity is associated with decreased global DNA methylation in Swedish older individuals. Scand J Clin Lab Invest. 2013;73:184-5.
140. Kanwal R, Gupta S. Epigenetics and cancer. J Appl Physiol. 2010;109:598-605.
141. Chalitchagorn K, Shuangshoti S, Hourpai N, et al. Distinctive pattern of LINE-1 methylation level in normal tissues and the association with carcinogenesis. Oncogene. 2004;23:8841-6.
142. Coyle YM, Xie XJ, Lewis CM, et al. Role of physical activity in modulating breast cancer risk as defined by APC and RASSF1A promoter hypermethylation in nonmalignant breast tissue. Cancer Epidemiol Biomarkers Prev. 2007;16:192-6.
143. Yuasa Y, Nagasaki H, Akiyama Y, et al. DNA methylation status is inversely correlated with green tea intake and physical activity in gastric cancer patients. Int J Cancer. 2009;124:2677-82.
144. Slattery ML, Curtin K, Sweeney C, et al. Diet and lifestyle factor associations with CpG island methylator phenotype and BRAF mutations in colon cancer. Int J Cancer. 2007;120:656-63.
145. Hughes LA, Simons CC, van den Brandt PA, et al. Body size, physical activity and risk of colorectal cancer with or without the CpG island methylator phenotype (CIMP). PLoS One. 2011;6:e18571.
146. Bryan AD, Magnan RE, Hooper AE, et al. Physical activity and differential methylation of breast cancer genes assayed from saliva: a preliminary investigation. Ann Behav Med. 2013;45:89-98.
147. Moleres A, Campion J, Milagro FI, et al. Differential DNA methylation patterns between high and low responders to a weight loss intervention in overweight or obese adolescents: the EVASYON study. FASEB J. 2013;27:2504-12.
148. Carone BR, Fauquier L, Habib N, et al. Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell. 2010;143:1084-96.
149. Morgan HD, Sutherland HG, Martin DI, et al. Epigenetic inheritance at the agouti locus in the mouse. Nat Genet. 1999;23:314-8.
150. Wolff GL, Kodell RL, Moore SR, et al. Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice. FASEB J. 1998;12:949-57.
151. Anway MD, Cupp AS, Uzumcu M, et al. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science. 2005;308:1466-9.
152. Guerrero-Bosagna C, Settles M, Lucker B, Skinner MK, et al. Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome. PLoS One. 2010;5(9).
153. Cooney CA, Dave AA, Wolff GL. Maternal methyl supplements in mice affect epigenetic variation and DNA methylation of offspring. J Nutr. 2002;132:2393S-400S.
154. Burdge GC, Slater-Jefferies J, Torrens C, et al. Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations. Br J Nutr. 2007;97:435-9.
155. Chen PY, Ganguly A, Rubbi L, et al. Intrauterine calorie restriction affects placental DNA methylation and gene expression. Physiol Genomics. 2013;45:565-76.
156. Soubry A, Schildkraut JM, Murtha A, et al. Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort. BMC Med. 2013;11:29.
157. Radom-Aizik S, Zaldivar F Jr, Leu SY, et al. Effects of exercise on microRNA expression in young males peripheral blood mononuclear cells. Clin Transl Sci. 2012;5:32-8.
158. Radom-Aizik S, Zaldivar FP, Haddad F, et al. Impact of brief exercise on peripheral blood NK cell gene and microRNA expression in young adults. J Appl Physiol. 2013;114:628-36.
159. Baggish AL, Hale A, Weiner RB, et al. Dynamic regulation of circulating microRNA during acute exhaustive exercise and sustained aerobic exercise training. J Physiol. 2011;589:3983-94.
160. Nielsen S, Scheele C, Yfanti C, et al. Muscle specific microRNAs are regulated by endurance exercise in human skeletal muscle. J Physiol. 2010;588:4029-37.
161. Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 2002;25:295-301.
162. Jacobs PL, Nash MS. Exercise recommendations for individuals with spinal cord injury. Sports Med. 2004;34:727-51.
163. Liu G, Detloff MR, Miller KN, et al. Exercise modulates microRNAs that affect the PTEN/mTOR pathway in rats after spinal cord injury. Exp Neurol. 2012;233:447-56.
164. Mojtahedi S, Kordi M, Soleimani M, et al. Effect of different intensities of short term aerobic exercise on expression of miR-124 in the hippocampus of adult male rats. J Res Med Sci. 2012;14:16-20.
165. Fernandes T, Soci UP, Oliveira EM. Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants. Braz J Med Biol Res. 2011;44:836-47.
166. Gielen S, Schuler G, Adams V. Cardiovascular effects of exercise training: molecular mechanisms. Circulation. 2010;122:1221-38.
167. Soci UP, Fernandes T, Hashimoto NY, et al. MicroRNAs 29 are involved in the improvement of ventricular compliance promoted by aerobic exercise training in rats. Physiol Genomics. 2011;43:665-73.
168. Fernandes T, Hashimoto NY, Magalhaes FC, et al. Aerobic exercise training-induced left ventricular hypertrophy involves regulatory microRNAs, decreased angiotensin-converting enzyme-angiotensin ii, and synergistic regulation of angiotensin-converting enzyme 2-angiotensin (1-7). Hypertension. 2011;58:182-9.
169. Ma Z, Qi J, Meng S, et al. Swimming exercise training-induced left ventricular hypertrophy involves microRNAs and synergistic regulation of the PI3K/AKT/mTOR signaling pathway. Eur J Appl Physiol. 2013;113(10):2473-86.
170. Moulton KS. Angiogenesis in atherosclerosis: gathering evidence beyond speculation. Curr Opin Lipidol. 2006;17:548-55.
171. Fernandes T, Magalhaes FC, Roque FR, et al. Exercise training prevents the microvascular rarefaction in hypertension balancing angiogenic and apoptotic factors: role of microRNAs-16, -21, and -126. Hypertension. 2012;59:513-20.
172. Wang S, Aurora AB, Johnson BA, et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 2008;15:261-71.
173. Fish JE, Santoro MM, Morton SU, et al. miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell. 2008;15:272-84.
174. da Silva NDJ, Fernandes T, Soci UP, et al. Swimming training in rats increases cardiac MicroRNA-126 expression and angiogenesis. Med Sci Sports Exerc. 2012;44:1453-62.
175. Yang Y, Creer A, Jemiolo B, et al. Time course of myogenic and metabolic gene expression in response to acute exercise in human skeletal muscle. J Appl Physiol. 2005;98:1745-52.
176. Phillips BE, Hill DS, Atherton PJ. Regulation of muscle protein synthesis in humans. Curr Opin Clin Nutr Metab Care. 2012;15:58-63.
177. Raue U, Slivka D, Jemiolo B, et al. Myogenic gene expression at rest and after a bout of resistance exercise in young (18-30 yr) and old (80-89 yr) women. J Appl Physiol. 2006;101:53-9.
178. Davidsen PK, Gallagher IJ, Hartman JW, et al. High responders to resistance exercise training demonstrate differential regulation of skeletal muscle microRNA expression. J Appl Physiol. 2011;110:309-17.
179. Mueller M, Breil FA, Lurman G, et al. Different molecular and structural adaptations with eccentric and conventional strength training in elderly men and women. Gerontology. 2011;57:528-38.
180. McCarthy JJ, Esser KA. MicroRNA-1 and microRNA-133a expression are decreased during skeletal muscle hypertrophy. J app physiol. 2007;102:306-13.
181. Drummond MJ, McCarthy JJ, Sinha M, et al. Aging and microRNA expression in human skeletal muscle: a microarray and bioinformatics analysis. Physiol Genomics. 2011;43:595-603.
182. Liang R, Bates DJ, Wang E. Epigenetic control of microRNA expression and aging. Curr Genomics. 2009;10:184-93.
183. Lu L, Zhou L, Chen EZ, et al. A novel YY1-miR-1 regulatory circuit in skeletal myogenesis revealed by genome-wide prediction of YY1-miRNA network. PLoS One. 2012;7:e27596.
184. Chen JF, Tao Y, Li J, et al. microRNA-1 and microRNA-206 regulate skeletal muscle satellite cell proliferation and differentiation by repressing Pax7. J Cell Biol. 2010;190:867-79.
185. Sun Y, Ge Y, Drnevich J, et al. Mammalian target of rapamycin regulates miRNA-1 and follistatin in skeletal myogenesis. J Cell Biol. 2010;189:1157-69.
186. Safdar A, Abadi A, Akhtar M, et al. miRNA in the regulation of skeletal muscle adaptation to acute endurance exercise in C57Bl/6 J male mice. PLoS One. 2009;4:e5610.
187. Rico-Sanz J, Rankinen T, Rice T, et al. Quantitative trait loci for maximal exercise capacity phenotypes and their responses to training in the HERITAGE Family Study. Physiol Genomics. 2004;16:256-60.
188. Macarthur DG, North KN. Genes and human elite athletic performance. Hum Genet. 2005;116:331-9.
189. McCarthy JJ, Esser KA, Peterson CA, et al. Evidence of MyomiR network regulation of β-myosin heavy chain gene expression during skeletal muscle atrophy. Physiol Genomics. 2009;39:219-26.
190. Aoi W, Naito Y, Mizushima K, et al. The microRNA miR-696 regulates PGC-1α in mouse skeletal muscle in response to physical activity. Am J Physiol Endocrinol Metab. 2010;298:e799-806.
191. Mendell JT, Olson EN. MicroRNAs in stress signaling and human disease. Cell. 2012;148:1172-87.
192. Chinsomboon J, Ruas J, Gupta RK, et al. The transcriptional coactivator PGC-1α mediates exercise-induced angiogenesis in skeletal muscle. Proc Natl Acad Sci USA. 2009;106:21401-6.
193. Lin J, Wu H, Tarr PT, et al. Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres. Nature. 2002;418:797-801.
194. Aquilano K, Vigilanza P, Baldelli S, et al. Peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1α) and sirtuin 1 (SIRT1) reside in mitochondria: possible direct function in mitochondrial biogenesis. J Biol Chem. 2010;285:21590-9.
195. Wu Z, Puigserver P, Andersson U, et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell. 1999;98:115-24.
196. Baoutina A, Alexander IE, Rasko JE, et al. Potential use of gene transfer in athletic performance enhancement. Mol Ther. 2007;15:1751-66.
197. Yamamoto H, Morino K, Nishio Y, et al. MicroRNA (miRNA)-494 regulates mitochondrial biogenesis in skeletal muscle through mitochondrial transcriptional factor A (mtTFA) and forkhead box j3 (Foxj3). Am J Physiol Endocrinol Metab. 2012;303:e1419-27.
198. Bye A, Rosjo H, Aspenes ST, et al. Circulating microRNAs and aerobic fitness - The HUNT-Study. PLoS One. 2013;8:e57496.
199. Aoi W, Ichikawa H, Mune K, et al. Muscle-enriched microRNA miR-486 decreases in circulation in response to exercise in young men. Front Physiol. 2013;4:80.
200. Kanaan Z, Rai SN, Eichenberger MR, et al. Plasma miR-21: a potential diagnostic marker of colorectal cancer. Ann Surg. 2012;256:544-51.
201. Uhlemann M, Mobius-Winkler S, Fikenzer S, et al. Circulating microRNA-126 increases after different forms of endurance exercise in healthy adults. Eur J Prev Cardiol. Epub 2012 Nov 13.
202. Radom-Aizik S, Zaldivar F Jr, Oliver S, et al. Evidence for microRNA involvement in exercise-associated neutrophil gene expression changes. J Appl Physiol. 2010;109:252-61.
203. Tonevitsky AG, Maltseva DV, Abbasi A, et al. Dynamically regulated miRNA-mRNA networks revealed by exercise. BMC Physiol. 2013;13:e9.
204. Sawada S, Kon M, Wada S, et al. Profiling of circulating microRNAs after a bout of acute resistance exercise in humans. PLoS One. 2013;8:e70823.
205. Marcus BH, Bock BC, Pinto BM, et al. Efficacy of an individualized, motivationally-tailored physical activity intervention. Ann Behav Med. 1998;20:174-80.