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• W3037214432 abstract "Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease. Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease. Exercise perturbs multiple systems from the whole body to the molecular level in an integrated manner (Hawley et al., 2014Hawley J.A. Hargreaves M. Joyner M.J. Zierath J.R. Integrative biology of exercise.Cell. 2014; 159: 738-749Abstract Full Text Full Text PDF PubMed Scopus (575) Google Scholar). However, in-depth fundamental knowledge into the molecular and cellular mechanisms that are responsible for physical activity’s benefits on multiple organ systems and the diseases and disorders that derive from inactivity is incomplete (Booth et al., 2017Booth F.W. Roberts C.K. Thyfault J.P. Ruegsegger G.N. Toedebusch R.G. Role of Inactivity in Chronic Diseases: Evolutionary Insight and Pathophysiological Mechanisms.Physiol. Rev. 2017; 97: 1351-1402Crossref PubMed Scopus (299) Google Scholar, Neufer et al., 2015Neufer P.D. Bamman M.M. Muoio D.M. Bouchard C. Cooper D.M. Goodpaster B.H. Booth F.W. Kohrt W.M. Gerszten R.E. Mattson M.P. et al.Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits.Cell Metab. 2015; 22: 4-11Abstract Full Text Full Text PDF PubMed Scopus (251) Google Scholar). A better understanding of these biological processes and pathways would allow for the development of targeted exercise interventions and prescriptions and provide a foundation for developing exercise-mimetic pharmacologic interventions. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to elucidate how exercise improves health and ameliorates diseases by building a map of the molecular responses to acute and chronic exercise. In 2014, a portfolio analysis of National Institutes of Health (NIH) grants revealed that most research regarding physical activity involved disease prevention or treatment. In fact, almost all the grants which employed an exercise intervention only addressed health outcomes and adherence issues. The MoTrPAC initiative provides a much needed comprehensive program to understand the interplay between these biological systems with the goal of improving the design of physical activity interventions. In addition, there is a potential to identify molecular targets that can be manipulated to mimic the effects of exercise in persons unable to do so for a variety of reasons, such as physical disability, coma, or paralysis. To address the gaps in knowledge about how exercise enhances health and ameliorates disease, multiple agencies at the NIH—including the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute on Aging (NIA), and other institutes and centers who participated in the trans-NIH Exercise Interest Group—proposed the Common Fund program supporting MoTrPAC. To create a substantive complex map of molecular transducers in diverse populations across the lifespan, MoTrPAC established a multi-site collaboration across the United States encompassing various scientific disciplines: preclinical animal study sites and human clinical exercise sites to perform the exercise testing, exercise interventions, and biospecimen collection; a consortium coordinating center to manage sample collection, distribution of samples, and consortium logistics; chemical analysis sites to perform ‘omics analysis from the samples collected; and a bioinformatics center to collaboratively facilitate data quality control, bioinformatics analysis, and dissemination to make the data and related resources available to the broad scientific community (Figure 1). The animal studies will enable analysis of the effects of exercise on many different tissues that are not readily obtainable in humans, thereby enabling a broad view of the systemic effects of exercise. The collection of human specimens (blood, muscle, and adipose) will permit the analysis of these critical systems, which are central to the energetics of exercise and appear to interact in a coordinated manner to improve overall metabolic health (Pedersen and Febbraio, 2012Pedersen B.K. Febbraio M.A. Muscles, exercise and obesity: skeletal muscle as a secretory organ.Nat. Rev. Endocrinol. 2012; 8: 457-465Crossref PubMed Scopus (1687) Google Scholar, Romijn et al., 1993Romijn J.A. Coyle E.F. Sidossis L.S. Gastaldelli A. Horowitz J.F. Endert E. Wolfe R.R. Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration.Am. J. Physiol. 1993; 265: E380-E391PubMed Google Scholar, Stanford and Goodyear, 2018Stanford K.I. Goodyear L.J. Muscle-Adipose Tissue Cross Talk.Cold Spring Harb. Perspect. Med. 2018; 8: a029801Crossref PubMed Scopus (61) Google Scholar). In addition to providing information concerning the effects of exercise at different physiological and molecular levels, the large scope of this study (humans: N = ∼2,600; rats: N = 820) will create a complex, integrative dataset that will be available to the scientific community. This dataset and some associated biospecimens can be leveraged by other groups by proposing ancillary studies to MoTrPAC. A primary goal of the Preclinical Animal Study Sites (PASSs) investigations is to enable the analysis of the systemic effects of exercise across many different organs and blood, most of which cannot be collected in humans. The first phase of the PASS studies is being conducted across three separate sites, with each collecting numerous biospecimens after acute (i.e., single bout) treadmill exercise or chronic treadmill training of male and female F344 rats at 6 and 18 months of age (Figure 2). For both acute and chronic exercise studies, the same biospecimens are being collected from non-exercised, control animals; for the acute studies this includes groups accounting for potential effects of time of day and time of feeding. This rat strain was selected for MoTrPAC because there is a large body of previous exercise research utilizing this strain, and rats provide larger amounts of tissue in contrast to mice. Larger tissue samples allow for multiple assays to be performed on the same sample, which supports bioinformatics analysis for the development of the molecular map of exercise. Also, larger tissues will provide additional material for ancillary studies. To control variation across the three PASSs, the rats are being provided from the same NIA colony, and the housing and feeding conditions are standardized across the sites. Furthermore, because rats are most active during the “dark” light phase, all rats are first being acclimated to a reverse light cycle for a minimum of 10 days, and with all exercise bouts conducted during the dark cycle. The PASS study design for the acute response to exercise entails a single 30-min bout of treadmill running (intensity: ∼80%–90% VO2max; incline: 5°; speed: 6 months: male – 16.8 m/min, female – 18.0 m/min; 18 months: male – 12.0 m/min, female – 13.8 m/min), with tissue collections occurring immediately post-exercise and at six additional times up to 48 h after the exercise bout. This sampling series is weighted toward early time points (0, 0.5, 1, and 4 h post-exercise) to capture the temporal dynamics of the molecular responses, but it also includes later time points (7, 24, and 48 h post-exercise) to capture long-duration primary responses as well as secondary molecular events (detailed protocols are available at https://motrpac.org/protocols.cfm). To study the biological events that occur during the early, intermediate, and later stages of endurance training, the PASS study design for the chronic response to exercise, which has been completed, entailed up to 8 weeks of treadmill training (5 days per week at ∼70% VO2max), with tissues collected 48 h after 1, 2, 4, and 8 weeks of training; incline, duration, and speed of exercise progressively increased on a daily to weekly basis during the initial 6 weeks of training. Sex differences in both the acute exercise response and the training response are being investigated along with other study aims. The most powerful aspect of the PASS design is the breadth of tissues collected. In addition to being studied in the context of MoTrPAC, these will serve as a data resource for generating hypotheses for future studies. For both the acute exercise and chronic exercise training studies (including the non-exercise controls), as many as 27 biospecimens per rat are being collected for potential analysis. In addition to biospecimen collection, other phenotypic outcomes are being collected, including blood lactate concentration, maximal oxygen consumption (VO2max), and body composition. At Chemical Analysis Sites, initial biospecimens of focus will include those that overlap with the human studies (i.e., plasma, skeletal muscle, white adipose), as well as liver, heart, kidney, lungs, brain, and brown adipose. It is expected that nucleic acid, proteomic, and targeted metabolomic assays will be performed only on tissues where the amount is non-limiting, whereas transcriptomics, non-targeted metabolomics, and non-targeted lipidomics will be performed on all tissues. Together, these assays are expected to provide molecular and physiological insights about the effect of exercise on many different organs. Ultimately, MoTrPAC should begin to explain how molecular transducers function across an entire mammal (Pedersen and Febbraio, 2012Pedersen B.K. Febbraio M.A. Muscles, exercise and obesity: skeletal muscle as a secretory organ.Nat. Rev. Endocrinol. 2012; 8: 457-465Crossref PubMed Scopus (1687) Google Scholar). After preliminary characterization of the changes that occur in the initial set of analyses, a second phase of the PASS will include mechanistic studies of exercise-induced molecules that transduce stress resistance and circulating factors that might be implicated in the health benefits of exercise. Additional studies will focus on the adaptation to chronic resistance exercise and the impact of age and sex on these responses, as well as other studies that have yet to be determined. The human component of MoTrPAC is an in-depth study of the effects of two different forms of exercise (endurance and resistance training) across multiple individuals of different ages (including children) and sexes, as well as sedentary and highly active individuals. This large cohort will be used to study the response to exercise at the whole body and cellular levels and attempt to identify the molecular underpinnings that might be responsible for the adaptive process and variation among individuals. Several traditional methods from the field of exercise physiology will be combined with novel biospecimen sampling and high-throughput molecular analytical approaches that will likely yield important insights into the effects of exercise on health. The human study has many unique aspects that are highlighted below and will be conducted as a randomized controlled trial (RCT) with an intent-to-treat design. The goal is to recruit 270 children and adolescents (10–17 years of age) who are low-active in endurance-type exercise and 1,980 healthy sedentary adults (age 18 years or greater) who will be medically screened and randomly assigned to endurance training (170 youth, 840 adults), resistance training (840 adults), or non-exercise control (50 youth, 300 adults) (Figure 2). An additional group of highly active endurance- (50 youth, 150 adults) and resistance- (150 adults) trained individuals will serve as comparators and will not participate in the MoTrPAC exercise training programs. The recruitment and enrollment approach will be sex balanced and provide participants across a wide range of ages (10–17, 18–39, 40–59 and ≥60 year age groups) and of different races. The sedentary adult participants randomized to endurance or resistance exercise training will perform 12 weeks of supervised exercise, 3 days per week, with progression in both volume and intensity. Each endurance training session will be ∼1 h in duration and be evenly split between cycling and treadmill (walking/running) exercise with intensity set to ∼60%–80% of heart rate reserve and monitored in real time during each session. Each resistance training session will target the whole body and consist of eight total exercises (five upper body: chest press, military press, seated row, triceps extension, biceps curl; three lower body: leg press, leg curl, knee extension) at a prescribed plan of 3 sets of 8–12 repetitions at an intensity of ∼60%–80% of maximum for each exercise. These exercise protocols are well known to improve clinically relevant parameters (i.e., VO2max and muscular strength and hypertrophy) via alterations in metabolic, biochemical, and molecular signatures (Coggan et al., 1990Coggan A.R. Kohrt W.M. Spina R.J. Bier D.M. Holloszy J.O. Endurance training decreases plasma glucose turnover and oxidation during moderate-intensity exercise in men.J. Appl. Physiol. 1990; 68: 990-996Crossref PubMed Scopus (160) Google Scholar, Gollnick et al., 1973Gollnick P.D. Armstrong R.B. Saltin B. Saubert 4th, C.W. Sembrowich W.L. Shepherd R.E. Effect of training on enzyme activity and fiber composition of human skeletal muscle.J. Appl. Physiol. 1973; 34: 107-111Crossref PubMed Scopus (452) Google Scholar, Raue et al., 2012Raue U. Trappe T.A. Estrem S.T. Qian H.-R. Helvering L.M. Smith R.C. Trappe S. Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults.J. Appl. Physiol. 2012; 112: 1625-1636Crossref PubMed Scopus (154) Google Scholar, Rönn et al., 2014Rönn T. Volkov P. Tornberg A. Elgzyri T. Hansson O. Eriksson K.-F. Groop L. Ling C. Extensive changes in the transcriptional profile of human adipose tissue including genes involved in oxidative phosphorylation after a 6-month exercise intervention.Acta Physiol. (Oxf.). 2014; 211: 188-200Crossref PubMed Scopus (48) Google Scholar, Timmons et al., 2010Timmons J.A. Knudsen S. Rankinen T. Koch L.G. Sarzynski M. Jensen T. Keller P. Scheele C. Vollaard N.B.J. Nielsen S. et al.Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans.J. Appl. Physiol. 2010; 108: 1487-1496Crossref PubMed Scopus (257) Google Scholar). A unique feature of the MoTrPAC adult protocol will be the integration of strategic biospecimen collections (blood, muscle, and adipose) before, during, and after standardized bouts of acute exercise. Participants will perform a 40 to 45-min bout of exercise (exercise-mode specific; rest for the non-exercise controls) with biospecimens collected before and after 12 weeks of training. The highly active group will perform the exercise-mode specific bout only once. Compared to resting homeostasis, these types of exercise challenges are expected to dramatically increase metabolic rate ∼5- to 10-fold (Coggan et al., 1990Coggan A.R. Kohrt W.M. Spina R.J. Bier D.M. Holloszy J.O. Endurance training decreases plasma glucose turnover and oxidation during moderate-intensity exercise in men.J. Appl. Physiol. 1990; 68: 990-996Crossref PubMed Scopus (160) Google Scholar, Farinatti and Castinheiras Neto, 2011Farinatti P.T.V. Castinheiras Neto A.G. The effect of between-set rest intervals on the oxygen uptake during and after resistance exercise sessions performed with large- and small-muscle mass.J. Strength Cond. Res. 2011; 25: 3181-3190Crossref PubMed Scopus (24) Google Scholar, Mulla et al., 2000Mulla N.A. Simonsen L. Bülow J. Post-exercise adipose tissue and skeletal muscle lipid metabolism in humans: the effects of exercise intensity.J. Physiol. 2000; 524: 919-928Crossref PubMed Scopus (81) Google Scholar, Romijn et al., 1993Romijn J.A. Coyle E.F. Sidossis L.S. Gastaldelli A. Horowitz J.F. Endert E. Wolfe R.R. Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration.Am. J. Physiol. 1993; 265: E380-E391PubMed Google Scholar), bioenergetic flux >10-fold (Kjaer et al., 1991Kjaer M. Kiens B. Hargreaves M. Richter E.A. Influence of active muscle mass on glucose homeostasis during exercise in humans.J. Appl. Physiol. 1991; 71: 552-557Crossref PubMed Scopus (92) Google Scholar, Romijn et al., 1993Romijn J.A. Coyle E.F. Sidossis L.S. Gastaldelli A. Horowitz J.F. Endert E. Wolfe R.R. Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration.Am. J. Physiol. 1993; 265: E380-E391PubMed Google Scholar, Steensberg et al., 2000Steensberg A. van Hall G. Osada T. Sacchetti M. Saltin B. Klarlund Pedersen B. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6.J. Physiol. 2000; 529: 237-242Crossref PubMed Scopus (730) Google Scholar), and large dynamic range in gene expression from small to >100-fold changes (Louis et al., 2007Louis E. Raue U. Yang Y. Jemiolo B. Trappe S. Time course of proteolytic, cytokine, and myostatin gene expression after acute exercise in human skeletal muscle.J. Appl. Physiol. 2007; 103: 1744-1751Crossref PubMed Scopus (341) Google Scholar, Radom-Aizik et al., 2013Radom-Aizik S. Zaldivar F. Haddad F. Cooper D.M. Impact of brief exercise on peripheral blood NK cell gene and microRNA expression in young adults.J. Appl. Physiol. 2013; 114: 628-636Crossref PubMed Scopus (82) Google Scholar, Radom-Aizik et al., 2014Radom-Aizik S. Zaldivar Jr., F.P. Haddad F. Cooper D.M. Impact of brief exercise on circulating monocyte gene and microRNA expression: implications for atherosclerotic vascular disease.Brain Behav. Immun. 2014; 39: 121-129Crossref PubMed Scopus (79) Google Scholar) and likely enhance cross-talk among many organs (Pedersen and Febbraio, 2012Pedersen B.K. Febbraio M.A. Muscles, exercise and obesity: skeletal muscle as a secretory organ.Nat. Rev. Endocrinol. 2012; 8: 457-465Crossref PubMed Scopus (1687) Google Scholar). Standardized conditions that control for physical activity, time of day, and dietary intake will be implemented prior to the acute exercise bout. On the day of an acute exercise bout with biospecimen collections, volunteers will arrive at a Human Clinical Center in the morning after an overnight fast and rest comfortably for 0.5 h prior to obtaining baseline blood (antecubital vein), skeletal muscle (vastus lateralis), and adipose (periumbilical region) samples. Participants will then perform the standardized acute exercise bout (or rest for the non-exercise control group) with additional biospecimen samples (blood, muscle, adipose) obtained ∼0.5 h (early), ∼4 h (middle), and ∼24 h (late) after exercise. These time points were chosen to capture the dynamic changes in the response to exercise as metabolic, post-translational, and epigenetic modifications can occur quite rapidly (Barrès et al., 2012Barrès R. Yan J. Egan B. Treebak J.T. Rasmussen M. Fritz T. Caidahl K. Krook A. O’Gorman D.J. Zierath J.R. Acute exercise remodels promoter methylation in human skeletal muscle.Cell Metab. 2012; 15: 405-411Abstract Full Text Full Text PDF PubMed Scopus (602) Google Scholar, Bolster et al., 2003Bolster D.R. Kubica N. Crozier S.J. Williamson D.L. Farrell P.A. Kimball S.R. Jefferson L.S. Immediate response of mammalian target of rapamycin (mTOR)-mediated signalling following acute resistance exercise in rat skeletal muscle.J. Physiol. 2003; 553: 213-220Crossref PubMed Scopus (178) Google Scholar, Hoffman et al., 2015Hoffman N.J. Parker B.L. Chaudhuri R. Fisher-Wellman K.H. Kleinert M. Humphrey S.J. Yang P. Holliday M. Trefely S. Fazakerley D.J. et al.Global Phosphoproteomic Analysis of Human Skeletal Muscle Reveals a Network of Exercise-Regulated Kinases and AMPK Substrates.Cell Metab. 2015; 22: 922-935Abstract Full Text Full Text PDF PubMed Scopus (251) Google Scholar, Romijn et al., 1993Romijn J.A. Coyle E.F. Sidossis L.S. Gastaldelli A. Horowitz J.F. Endert E. Wolfe R.R. Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration.Am. J. Physiol. 1993; 265: E380-E391PubMed Google Scholar), whereas mRNA induction generally peaks a few hours after exercise (Louis et al., 2007Louis E. Raue U. Yang Y. Jemiolo B. Trappe S. Time course of proteolytic, cytokine, and myostatin gene expression after acute exercise in human skeletal muscle.J. Appl. Physiol. 2007; 103: 1744-1751Crossref PubMed Scopus (341) Google Scholar, Yang et al., 2005Yang Y. Creer A. Jemiolo B. Trappe S. Time course of myogenic and metabolic gene expression in response to acute exercise in human skeletal muscle.J. Appl. Physiol. 2005; 98: 1745-1752Crossref PubMed Scopus (195) Google Scholar), and increases in protein synthesis rates are detectable in the hours and days following exercise (Phillips et al., 1997Phillips S.M. Tipton K.D. Aarsland A. Wolf S.E. Wolfe R.R. Mixed muscle protein synthesis and breakdown after resistance exercise in humans.Am. J. Physiol. 1997; 273: E99-E107Crossref PubMed Google Scholar) (Figure 3). Additional blood samples will be collected during the endurance exercise bout (20- and 40-min time points) and shortly after (10 min) both endurance and resistance exercise bouts. All participants will have pre-exercise biospecimen collections, but to reduce participant burden in the post-exercise phase, sedentary participants will undergo skeletal muscle and adipose biopsies at one of three time points (early, middle, late). The highly active participants will have muscle biopsies and blood at all time points, whereas adipose biopsies will be collected at the pre and middle time points. Children and adolescents undergo critical periods of growth and development, which are distinct from adult physiology. Pediatric studies must also comply with additional ethical considerations (Radom-Aizik and Cooper, 2016Radom-Aizik S. Cooper D.M. Bridging the Gaps: the Promise of Omics Studies in Pediatric Exercise Research.Pediatr. Exerc. Sci. 2016; 28: 194-201Crossref PubMed Scopus (5) Google Scholar). Consequently, although the pediatric arm of the study will mimic the adult protocol as closely as possible, there are a few notable exceptions: (1) children who are low-active in endurance-type exercise will be recruited (versus sedentary adults) to account for the fact that children are naturally more active than adults and also participate in mandatory physical education classes; (2) no tissue biopsies (only blood will be collected); (3) an acute bout of endurance exercise with blood collection will be performed in both the training intervention and no-exercise control groups; (4) blood samples will be collected in all participants before, 20 and 40 min during exercise, and 10 min, 0.5 h, and 3.5 h into recovery; and (5) for a subgroup of 170 low-active endurance exercise children and adolescents who will be randomized to receive 12-week endurance training (N = 120) or continue their standard practice (N = 50) (Figure 2), the endurance exercise intervention will be modified to provide an exercise intervention that is appropriate to the pediatric participants’ age group. For middle and high school students the modes of endurance exercise will include cycling and treadmill and also an option for elliptical and rowing machines. Elementary school students will be trained in a form of circuit training (e.g., endurance activity stations: cycle ergometer, steppers, individual jump rope, pacer, and sliders) to keep the younger participants engaged. To complement the molecular map, selected phenotypic measures will be obtained. Participants will be assessed before and after the 12-week intervention period, whereas the highly active adult comparator group members will be assessed once. These measurements include maximal oxygen consumption on a cycle ergometer (VO2max), grip strength, maximal isometric knee extension strength, body composition (DXA, dual-energy X-ray absorptiometry), clinical blood profiles, heart rate profiles during the acute endurance and resistance exercise bouts, substrate utilization (carbohydrate and fat) during the acute endurance exercise bout at ∼65% VO2max (adult endurance participants only), and upper and lower body strength (one-repetition maximum; adult resistance participants only). Most of the adult participants also will provide information on self-reported health outcomes using PROMIS measures (www.nihpromis.org) that will provide opportunities to investigate the effect of exercise on mood, anxiety, and depression. In a subgroup of adult participants, skeletal muscle and adipose histology (cell type, size, capillarization) and single cell analysis across various ‘omics platforms will be conducted. Investigators are exploring the potential for collecting and analyzing microbiome samples from a subgroup of adult participants. To optimize this complex protocol, the adult component of the study will be implemented in two phases. The first phase will involve ∼150 adult participants and will require ∼4–6 months, enabling assessment of participant and clinical burden and feasibility, as well as allowing for refinement of the MoTrPAC protocol. In phase two, the remainder of the project with a target of over 2,000 participants will be implemented. The Consortium Coordinating Center (CCC) is composed of four parts: an Administrative Coordinating Center (ACC), a Data Management, Analysis and Quality Control (DMAQC) Core, an Exercise Intervention Core (EIC), and a central Biorepository. The role of the ACC is to enable the organization and governance of MoTrPAC by facilitating key processes such as meeting logistics, IRB submission, and preparation of Manuals of Operations. The Biorepository, working with the preclinical and clinical sites, the DMAQC, and the Chemical Analysis Sites, oversees sample collection, shipping, archiving, and distribution of human and animal samples. This includes ensuring that homogeneous cryo-pulverization of tissue samples occurs prior to distribution of aliquots to the various Chemical Analysis Sites. Uniform sample processing is important to ensure that diverse data types can be directly compared. Each tissue sample will also be stored for future use by MoTrPAC and non-MoTrPAC investigators. Samples include serum, EDTA plasma, PAXgene-protected whole blood and peripheral blood mononuclear cells, and vastus lateralis skeletal muscle and subcutaneous abdominal adipose tissue from humans and >20 different tissues from the preclinical animals. Each sample will be analyzed by the Chemical Analysis Sites, and additional material will be archived for future use. The Biorepository inventory system interacts with the DMAQC to enable sample tracking, quality control, and other process support systems. To understand the exercise response in detail, an in-depth analysis of molecular and ‘omic assays will be performed using state-of-the-art laboratory techniques. Technologies include genomics, transcriptomics, DNA methylomics, targeted and untargeted proteomics, and targeted and untargeted metabolomics. Evidence has shown, through more than 150 small cohort studies (typically with under 50 participants analyzed) (Bouchard et al., 2011Bouchard C. Rankinen T. Timmons J.A. Genomics and genetics in the biology of adaptation to exercise.Compr. Physiol. 2011; 1: 1603-1648PubMed Google Scholar, Pacheco et al., 2018Pacheco C. Felipe S.M.D.S. Soares M.M.D.C. Alves J.O. Soares P.M. Leal-Cardoso J.H. Loureiro A.C.C. Ferraz A.S.M. de Carvalho D.P. Ceccatto V.M. A compendium of physical exercise-related human genes: an 'omic scale analysis.Biol. Sport. 2018; 35: 3-11PubMed Google Scholar), that exercise is accompanied with massive changes at both the transcriptional and epigenomic levels in muscle, adipose, and most other tissue systems (Lindholm et al., 2014Lindholm M.E. Marabita F. Gomez-Cabrero D. Rundqvist H. Ekströ" @default.
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