1. Adams GR, Caiozzo VJ, Haddad F, Baldwin KM. Cellular and molecular responses to increased skeletal muscle loading after irradiation. Am J Physiol Cell Physiol. 2002;283:C1182–C1195. [PubMed] [Google Scholar]
2. Atherton PJ, Babraj JA, Smith K, Singh J, Rennie MJ, Wackerhage H. Selective activation of AMPK-PGC-1α or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation. FASEB J. 2005;19:786–788. [PubMed] [Google Scholar]
3. Baar K, Wende AR, Jones TE, et al. Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1. FASEB J. 2002;16:1879–1886. [PubMed] [Google Scholar]
4. Baldwin KM. Research in the exercise sciences: Where do we go from here? J Appl Physiol. 2000;88:332–336. [PubMed] [Google Scholar]
5. Blair SN, Cheng Y, Holder JS. Is physical activity or physical fitness more important in defining health benefits? Med Sci Sports Exerc. 2001;33 Suppl 6:S379–S399. [PubMed] [Google Scholar]
6. Bodine SC. mTOR Signaling and the Molecular Adaptation to Resistance Exercise. Med Sci Sports Exerc. 2006;38:1950–1957. [PubMed] [Google Scholar]
7. Booth FW, Laye MJ. Lack of adequate appreciation of physical exercise's complexities can pre-empt appropriate design and interpretation in scientific discovery. J Physiol. 2009 (In Press), doi: 10.1113/jphysiol.2009.179507. [PMC free article] [PubMed] [Google Scholar]
8. Bray MSHJ, Pérusse L, Rankinen T, Roth SM, Wolfarth B, Bouchard C. The Human Gene Map for Performance and Health-Related Fitness Phenotypes:The 2006–2007 Update. Med Sci Sports Exerc. 2009;41:35–73. [PubMed] [Google Scholar]
9. Brehm M, Picard F, Ebner P, et al. Effects of exercise training on mobilization and functional activity of blood-derived progenitor cells in patients with acute myocardial infarction. Eur J Med Res. 2009;14:393–405. [PMC free article] [PubMed] [Google Scholar]
10. Callis TE, Deng Z, Chen J-F, Wang D-Z. Muscling Through the microRNA World. Experimental Biology and Medicine. 2008;233:131–138. [PubMed] [Google Scholar]
11. Collins A, Hill LE, Chandramohan Y, Whitcomb D, Droste SK, Reul JMHM. Exercise Improves Cognitive Responses to Psychological Stress through Enhancement of Epigenetic Mechanisms and Gene Expression in the Dentate Gyrus. PLoS ONE. 2009;4:e4330. [PMC free article] [PubMed] [Google Scholar]
12. Favier F, Benoit H, Freyssenet D. Cellular and molecular events controlling skeletal muscle mass in response to altered use. Pflungers Archiv European J Physiol. 2008;456:587–600. [PubMed] [Google Scholar]
13. Fraser GE, Shavlik DJ. Ten Years of Life: Is It a Matter of Choice? Arch Intern Med. 2001;161:1645–1652. [PubMed] [Google Scholar]
14. Greenes RAMDP, Shortliffe EHMDP. Commentary: Informatics in Biomedicine and Health Care. Acad Med. 2009;84:818–820. [Editorial]. [PubMed] [Google Scholar]
15. Hamrick M, Skedros J, Pennington C, McNeil P. Increased osteogenic response to exercise in metaphyseal versus diaphyseal cortical bone. J Musculoskelet Neuronal Interact. 2006;6:258–263. [PubMed] [Google Scholar]
16. Hassan A. Potential applications of RNA interference-based therapeutics in the treatment of cardiovascular disease. Recent Pat Cardiovasc Drug Discov. 2006;1:141–149. [PubMed] [Google Scholar]
17. Hawley JA, Holloszy JO. Exercise: it's the real thing! Nutrition Reviews. 2009;67:172–178. [PubMed] [Google Scholar]
18. Holloszy JO. Biochemical Adaptations in Muscle. Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle. J Biol Chem. 1967;242:2278–2282. [PubMed] [Google Scholar]
19. Hollozsy J. Regulation by exercise of skeletal muscle content of mitochondria and GLUT4. J Physiol Pharmacol. 2008;59 Suppl.7:5–18. [PubMed] [Google Scholar]
20. Hood D. Mechanisms of exercise-induced mitochondrial biogenesis in skeletal muscle. Appl Physiol Nutr Metab. 2009;34:465–472. [PubMed] [Google Scholar]
21. Howlett RA, Kirkton SD, Gonzalez NC, et al. Peripheral oxygen transport and utilization in rats following continued selective breeding for endurance running capacity. J Appl Physiol. 2009;106:1819–1825. [PMC free article] [PubMed] [Google Scholar]
22. Huber K, Miles JL, Norman AM, Thompson NM, Davison M, Breier BH. Prenatally Induced Changes in Muscle Structure and Metabolic Function Facilitate Exercise-Induced Obesity Prevention. Endocrinology. 2009;150:4135–4144. [PubMed] [Google Scholar]
23. Joyner MJ, Green DJ. Excersise protects the cardiovascular system: effects beyond traditional risk factors. The Journal of Physiology. 2009 (in press). doi: 10.1113/jphysiol.2009.179432. [PMC free article] [PubMed] [Google Scholar]
24. Kyle UG, Pichard C. The Dutch Famine of 1944–1945: a pathophysiological model of long-term consequences of wasting disease. Current Opinion in Clinical Nutrition & Metabolic Care. 2006;9:388–394. [PubMed] [Google Scholar]
25. Leick L, Wojtaszewski JFP, Johansen ST, et al. PGC-1{alpha} is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle. Am J Physiol Endocrinol Metab. 2008;294:E463–E474. [PubMed] [Google Scholar]
26. Lu PY, Xie F, Woodle MC. Non-Viral Vectors for Gene Therapy, Second Edition: Part 2. Volume 54 ed. Leaf Huang M-CH, and Ernst Wagner: Academic Press; 2005. In Vivo Application of RNA Interference: From Functional Genomics to Therapeutics. Advances in Genetics; pp. 115–142. [Google Scholar]
27. Mackey AL, Heinemeier KM, Anneli Koskinen SO, Kjaer M. Dynamic Adaptation of Tendon and Muscle Connective Tissue to Mechanical Loading. Connective Tissue Research. 2008;49:165–168. [PubMed] [Google Scholar]
28. Malek MH, Olfert IM. Global deletion of thrombospondin-1 increases cardiac and skeletal muscle capillarity and exercise capacity in mice. Exp Physiol. 2009;94:749–760. [PubMed] [Google Scholar]
29. Mammucari C, Schiaffino D, Sandri M. FoxO3 and mTOR in the regulation of autophagy in skeletal muscle. Autophagy. 2008;4:524–526. [PubMed] [Google Scholar]
30. Mehler MF. Epigenetics and the nervous system. Annals of Neurology. 2008;64:602–617. [PubMed] [Google Scholar]
31. Milagro FICJ, García-Díaz DF, Goyenechea E, Paternain L, Martínez JA. High fat diet-induced obesity modifies the methylation pattern of leptin promoter in rats. J Physiol Biochem. 2009;65:1–9. [PubMed] [Google Scholar]
32. Miyazaki M, Esser KA. Cellular mechanisms regulating protein synthesis and skeletal muscle hypertrophy in animals. J Appl Physiol. 2009;106:1367–1373. [PMC free article] [PubMed] [Google Scholar]
33. Moebius-Winkler S, Hilberg T, Menzel K, et al. Time Dependent Mobilization of Circulating Progenitor Cells During Strenuous Exercise in Healthy Individuals. J Appl Physiol. 2009;107(6):1943–1950. [PubMed] [Google Scholar]
34. Narkar VADM, Yu RT, Embler E, et al. AMPK and PPARdelta agonists are exercise mimetics. Cell. 2008;134:405–415. [PMC free article] [PubMed] [Google Scholar]
35. Pandorf CE, Haddad F, Roy RR, Qin AX, Edgerton VR, Baldwin KM. Dynamics of Myosin Heavy Chain Gene Regulation in Slow Skeletal Muscle: Role of Natural Antisense RNA. J Biol Chem. 2006;281:38330–38342. [PubMed] [Google Scholar]
36. Pandorf CE, Haddad F, Wright C, Bodell PW, Baldwin KM. Differential epigenetic modifications of histones at the myosin heavy chain genes in fast and slow skeletal muscle fibers and in response to muscle unloading. Am J Physiol Cell Physiol. 2009;297:C6–C16. [PMC free article] [PubMed] [Google Scholar]
37. Pedersen BK, Akerstrom TCA, Nielsen AR, Fischer CP. Role of myokines in exercise and metabolism. J Appl Physiol. 2007;103:1093–1098. [PubMed] [Google Scholar]
38. Petrella JK, Kim J-s, Mayhew DL, Cross JM, Bamman MM. Potent myofiber hypertrophy during resistance training in humans is associated with satellite cell-mediated myonuclear addition: a cluster analysis. J Appl Physiol. 2008;104:1736–1742. [PubMed] [Google Scholar]
39. Rehman J, Li J, Orschell CM, March KL. Peripheral Blood "Endothelial Progenitor Cells" Are Derived From Monocyte/Macrophages and Secrete Angiogenic Growth Factors. Circulation. 2003;107:1164–1169. [PubMed] [Google Scholar]
40. Riechman SE, Balasekaran G, Roth SM, Ferrell RE. Association of interleukin-15 protein and interleukin-15 receptor genetic variation with resistance exercise training responses. J Appl Physiol. 2004;97:2214–2219. [PubMed] [Google Scholar]
41. Rinaldi C, Haddad F, Bodell PW, Qin AX, Jiang W, Baldwin KM. Intergenic Bidirectional Promoter and Cooperative Regulation of the IIx and IIb MHC Genes in Fast Skeletal Muscle. Am J Physiol Regul Integr Comp Physiol. 2008;295:208–218. [PMC free article] [PubMed] [Google Scholar]
42. Roth SM. Perspective on the future use of genomics in exercise prescription. J Appl Physiol. 2008;104:1243–1245. [PubMed] [Google Scholar]
43. Sandri M, Sandri C, Gilbert A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell. 2004;117:399–412. [PMC free article] [PubMed] [Google Scholar]
44. Saunders M, Lim L. (micro)Genomic medicine: microRNAs as therapeutics and biomarkers. RNA Biol. 2009;6:324–328. [PubMed] [Google Scholar]
45. Suuriniemi M, Mahonen A, Kovanen V, et al. Association Between Exercise and Pubertal BMD Is Modulated by Estrogen Receptor alpha Genotype. Journal of Bone and Mineral Research. 2004;19:1758–1765. [PubMed] [Google Scholar]
46. Teramoto M, Bungum TJ. Mortality and longevity of elite athletes. Journal of Science and Medicine in Sport. 2009 (In Press) doi: 10.1016/j.jsams.2009.04.010. [PubMed] [Google Scholar]
47. Winder W, Thomson D. Cellular energy sensing and signaling by AMP-activated protein kinase. Cell Biochemistry and Biophysics. 2007;47:332–347. [PubMed] [Google Scholar]
48. Witkowski S, Lockard MM, Jenkins NT, Obisesan TO, E.Spangenburg E, Hagberg JM. Relationship between circulating progenitor cells to vascular function and oxidative stress with long term training and short term detraining in older men. Clin Sci. 2010;118:303–311. [PMC free article] [PubMed] [Google Scholar]
49. Yang N, Garton F, North K. alpha-Actinin-3 and Performance. Med Sport Sci. 2009;54:88–101. [PubMed] [Google Scholar]
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depicts two parallel tracts of research focus in exercise science: 1) genomics and gene regulation, and 2) basic biochemistry and physiology. These priorities should move synergistically with one another to insure that integrated function across several organ systems will unfold to derive the important outcomes of fitness, reduced disease potential, and longevity. The rationale for this scheme is depicted in the text material.