| 1. |
- Andersson, Urban, 1965, et al.
(författare)
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Research.chalmers.se : building the next generation research information infrastructure at Chalmers University of Technology
- 2016
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- research.chalmers.se is the new research infrastructure - repository platform and CRIS - that is currently being developed by the library at Chalmers University of Technology, Sweden.With the aim of eventually becoming the place for all relevant research information at the university, and built in accordance with the principles of UX (User eXperience) and agile development (SCRUM) and with a steady focus on value and continuous deliveries, research.chalmers.se is set to replace most of the current research information infrastructure at the university. It will provide new services for collecting, curating and providing quality data, as well as tools for analysis, sharing and promotion of research output by new and up-to-date means.research.chalmers.se is (or will be)- creating and preserving values - research output and data repository with qualitativedata, researcher profiles, open access.- promoting open access publishing, by proving the value of knowledge sharing, visibilityand impact as a researcher.- collecting and curating all kinds of research information, including publications,research data and information about research projects and other research activities.- built with responsive design that is adapted to current user needs. - using current standards for validity and sustainability, such as ORCID, DOI andFundRef IDs.- providing new ways of exploring and analyzing data, such as altmetrics, open APIs andvisualization tools.In the first phase (starting in 2014) a complete system for handling research project and grant information has been developed, together with integration of the local HR system for persistent and structured data about staff and organisation.In the current phase (2016-) repository services are being developed, such as a new publication database and a new digital repository, along with services for sharing and collecting data.The next phase(s) will include handling of research data, research activities, learning objects and tools for bibliometric analysis.This poster will show some of the current and future features and the principles of UX and agile development, as well as the experiences of moving out of the comfort zone and dealing with new, non-publication related data, while sustaining and enhancing existing data and current services. It will discuss the challenges and possible solutions, when handling different kinds of research information for use and re-use, in the long run enabling the comprehension of the big picture of research at Chalmers University of Technology.
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| 2. |
- Chapman, Mark A., et al.
(författare)
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Skeletal Muscle Transcriptomic Comparison between Long-Term Trained and Untrained Men and Women
- 2020
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 31:12
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Tidskriftsartikel (refereegranskat)abstract
- To better understand the health benefits of lifelong exercise in humans, we conduct global skeletal muscle transcriptomic analyses of long-term endurance- (9 men, 9 women) and strength-trained (7 men) humans compared with age-matched untrained controls (7 men, 8 women). Transcriptomic analysis, Gene Ontology, and genome-scale metabolic modeling demonstrate changes in pathways related to the prevention of metabolic diseases, particularly with endurance training. Our data also show prominent sex differences between controls and that these differences are reduced with endurance training. Additionally, we compare our data with studies examining muscle gene expression before and after a months-long training period in individuals with metabolic diseases, This analysis reveals that training shifts gene expression in individuals with impaired metabolism to become more similar to our endurance-trained group. Overall, our data provide an extensive examination of the accumulated transcriptional changes that occur with decades-long training and identify important "exercise-responsive" genes that could attenuate metabolic disease.
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| 3. |
- Emanuelsson, Eric B., et al.
(författare)
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Remodeling of the human skeletal muscle proteome found after long-term endurance training but not after strength training
- 2024
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 27:1
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Tidskriftsartikel (refereegranskat)abstract
- Exercise training has tremendous systemic tissue-specific health benefits, but the molecular adaptations to long-term exercise training are not completely understood. We investigated the skeletal muscle proteome of highly endurance-trained, strength-trained, and untrained individuals and performed exercise- and sex-specific analyses. Of the 6,000+ proteins identified, >650 were differentially expressed in endurance-trained individuals compared with controls. Strikingly, 92% of the shared proteins with higher expression in both the male and female endurance groups were known mitochondrial. In contrast to the findings in endurance-trained individuals, minimal differences were found in strength-trained individuals and between females and males. Lastly, a co-expression network and comparative literature analysis revealed key proteins and pathways related to the health benefits of exercise, which were primarily related to differences in mitochondrial proteins. This network is available as an interactive database resource where investigators can correlate clinical data with global gene and protein expression data for hypothesis generation.
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| 5. |
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| 6. |
- Lindholm, Malene E., et al.
(författare)
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The human skeletal muscle transcriptome : sex differences, alternative splicing, and tissue homogeneity assessed with RNA sequencing
- 2014
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 211, s. 38-38
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Tidskriftsartikel (refereegranskat)abstract
- Human skeletal muscle health is important for quality of life and several chronic diseases, including type II diabetes, heart disease, and cancer. Skeletal muscle is a tissue widely used to study mechanisms behind different diseases and adaptive effects of controlled interventions. For such mechanistic studies, knowledge about the gene expression profiles in different states is essential. Since the baseline transcriptome has not been analyzed systematically, the purpose of this study was to provide a deep reference profile of female and male skeletal muscle. RNA sequencing data were analyzed from a large set of 45 resting human muscle biopsies. We provide extensive information on the skeletal muscle transcriptome, including 5 previously unannotated protein-coding transcripts. Global transcriptional tissue homogeneity was strikingly high, within both a specific muscle and the contralateral leg. We identified >23,000 known isoforms and found >5000 isoforms that differ between the sexes. The female and male transcriptome was enriched for genes associated with oxidative metabolism and protein catabolic processes, respectively. The data demonstrate remarkably high tissue homogeneity and provide a deep and extensive baseline reference for the human skeletal muscle transcriptome, with regard to alternative splicing, novel transcripts, and sex differences in functional ontology.
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| 7. |
- Lindholm, Malene E., et al.
(författare)
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The Impact of Endurance Training on Human Skeletal Muscle Memory, Global Isoform Expression and Novel Transcripts
- 2016
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Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Regularly performed endurance training has many beneficial effects on health and skeletal muscle function, and can be used to prevent and treat common diseases e.g. cardiovascular disease, type II diabetes and obesity. The molecular adaptation mechanisms regulating these effects are incompletely understood. To date, global transcriptome changes in skeletal muscles have been studied at the gene level only. Therefore, global isoform expression changes following exercise training in humans are unknown. Also, the effects of repeated interventions on transcriptional memory or training response have not been studied before. In this study, 23 individuals trained one leg for three months. Nine months later, 12 of the same subjects trained both legs in a second training period. Skeletal muscle biopsies were obtained from both legs before and after both training periods. RNA sequencing analysis of all 119 skeletal muscle biopsies showed that training altered the expression of 3,404 gene isoforms, mainly associated with oxidative ATP production. Fifty-four genes had isoforms that changed in opposite directions. Training altered expression of 34 novel transcripts, all with protein-coding potential. After nine months of detraining, no training-induced transcriptome differences were detected between the previously trained and untrained legs. Although there were several differences in the physiological and transcriptional responses to repeated training, no coherent evidence of an endurance training induced transcriptional skeletal muscle memory was found. This human lifestyle intervention induced differential expression of thousands of isoforms and several transcripts from unannotated regions of the genome. It is likely that the observed isoform expression changes reflect adaptational mechanisms and processes that provide the functional and health benefits of regular physical activity.
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| 8. |
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| 9. |
- Lindholm, Maléne
(författare)
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The search for human skeletal muscle memory : exercise effects on the transcriptome and epigenome
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Regular physical activity is an environmental stimulus that is highly associated to many health benefits, while physical inactivity is detrimental for health and physical function. Regular exercise training is used in the prevention and treatment of a large number of disease conditions, including obesity, type II diabetes, cardiovascular disease and cancer, and reduces the risk for premature death. Most tissues adapt to exercise training, not least skeletal muscle tissue, which is highly plastic. The local adaptation of muscle is important not only for muscle function but also the health effects of training that affect the whole body. The cellular adaptations in skeletal muscle are driven by extra- and intracellular signals arising from the exercise stimulus, for example changes in shear stress, oxygen tension, energy levels, pH and temperature. Ultimately, these cellular perturbations lead to gene expression and protein alterations that improve muscle function. Thus, it is important from a clinical, as well as basic science perspective to understand the regulation of skeletal muscle gene activity and how activity changes contribute to the many health benefits of a physically active lifestyle. The understanding of training-induced changes in gene expression and the underlying mechanisms have progressed extensively over the past 20 years. Still, many key mechanisms remain to be investigated. The overall purpose of this thesis was to investigate the influence of epigenetic mechanisms, i.e. DNA methylation and post-translational modifications of histones, on endurance training adaptation. Epigenetic mechanisms are important for cellular memory. Thus, another objective was to investigate if there were any residual intrinsic memory effects of previous endurance training, and if that could induce different responses to a repeated training period after detraining. The results in this thesis are based on skeletal muscle biopsies from the vastus lateralis, taken before and after three months, or six weeks, of endurance training, or at rest in elite athletes and sedentary individuals. In the first study, the baseline skeletal muscle transcriptome was investigated. Studies using repeated skeletal muscle sampling regularly assume that potential changes are due to the intervention and not inherent variability between samples. The results showed, using global RNA sequencing analysis, that tissue homogeneity was remarkably high within a muscle and in the corresponding muscle of the contralateral leg of an individual, while the transcriptome difference between male and female skeletal muscle was substantial. This study also found 23 000 isoforms expressed in skeletal muscle at baseline, together with almost 2500 previously unannotated, novel transcripts, out of which at least five were protein-coding. The transcriptome changes induced by three months of one-legged knee extension training were very significant. Over 3000 isoforms were found to be differentially expressed, as well as 34 of the novel transcripts discovered at baseline. The one-legged training regime meant that the other leg was included as an intraindivdual control leg, which was exposed to the same other environmental factors such as diet, stress, sleep etc. We found that the training response of the trained leg was very specific, although significant but markedly smaller changes occurred also in the untrained leg. At the protein level, a specific investigation of HIF (hypoxia inducible factor) was performed. HIF is activated by acute exercise, but was hypothesized to be attenuated by long-term training due to its inhibitory effect on mitochondrial energy production. A comparison of skeletal muscle from elite athletes with normally active individuals, showed that the negative regulators of HIF were higher in the elite athletes, indicating a reduced HIF activity in that group. This was supported by similar findings in a six-week bicycle training study. Three months of endurance training induced changes in DNA methylation at almost 5000 specific sites across the human skeletal muscle genome that were associated to functionally relevant transcriptional changes. Many of these changes occurred in regulatory enhancer regions and the differentially methylated sites were associated to transcription factor binding sites for myogenic regulatory factors (increases in methylation) and the ETS family (decreases in methylation). Six weeks of bicycle training showed a strong trend towards a global downregulation of trimethylation of histone H3, lysine 27, previously described as a dynamic and predominantly inhibitory modification. The specific genes potentially affected by this histone modification in response to training are currently being analyzed using chromatin immunoprecipitation followed by sequencing. After the initial three months of one-legged endurance training, a subset of the subjects came back after nine months of detraining and performed a second three-month training period. This time, they trained both legs in the exact same way as one leg was trained in the first period. One leg had thus been previously well-trained, while the other was previously untrained. Potential residual effects were investigated by comparing biopsies obtained from both legs before starting the second training period. At the transcriptome level, there were no indications of remaining effects, although the exertion perceived in the first training session of period 2 was lower in the previously trained leg. Repeated training induced similar changes physiologically and at the global transcriptome level between the two legs. There were specific differences in the gene activity changes between the legs, but with the current approach, we found no overall significant differences in the response to a repeated training period. Collectively, the results in this thesis show that endurance exercise training induced associated changes in the epigenome and transcriptome of human skeletal muscle. The data included an in-depth analysis of the human skeletal muscle transcriptome at baseline and how it changes in response to repeated endurance training periods, with no detectable muscle memory of previous training at the transcriptome level. The results contribute to a better understanding of the molecular pathways involved in physiological adaptation to endurance training and can potentially be used to describe how training prevents disease development and different dysfunctions.
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| 10. |
- Lindskog, Cecilia, et al.
(författare)
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The human cardiac and skeletal muscle proteomes defined by transcriptomics and antibody-based profiling
- 2015
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: To understand cardiac and skeletal muscle function, it is important to define and explore their molecular constituents and also to identify similarities and differences in the gene expression in these two different striated muscle tissues. Here, we have investigated the genes and proteins with elevated expression in cardiac and skeletal muscle in relation to all other major human tissues and organs using a global transcriptomics analysis complemented with antibody-based profiling to localize the corresponding proteins on a single cell level. Results: Our study identified a comprehensive list of genes expressed in cardiac and skeletal muscle. The genes with elevated expression were further stratified according to their global expression pattern across the human body as well as their precise localization in the muscle tissues. The functions of the proteins encoded by the elevated genes are well in line with the physiological functions of cardiac and skeletal muscle, such as contraction, ion transport, regulation of membrane potential and actomyosin structure organization. A large fraction of the transcripts in both cardiac and skeletal muscle correspond to mitochondrial proteins involved in energy metabolism, which demonstrates the extreme specialization of these muscle tissues to provide energy for contraction. Conclusions: Our results provide a comprehensive list of genes and proteins elevated in striated muscles. A number of proteins not previously characterized in cardiac and skeletal muscle were identified and localized to specific cellular subcompartments. These proteins represent an interesting starting point for further functional analysis of their role in muscle biology and disease.
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| 11. |
- Mattsson, C. Mikael, et al.
(författare)
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The ELITE project (Exercise at the Limit - Inherited Traits of Endurance) - the genetic profiles of the best endurance athletes in the world.
- 2017
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Konferensbidrag (refereegranskat)abstract
- Cardiovascular health exists as a spectrum of wellness and disease states. Moreover, a significant portion of what defines these states is due to genetics. We hypothesize that there exist genes and pathways that dually contribute to both disease and extreme health states. Interrogating the ‘adaptive’ tail of the distribution for individuals with extreme phenotypes, such as high maximum oxygen uptake (VO2max) in endurance athletes, will inform prevention, cause and treatment of pathogenic (‘maladaptive’) conditions. 1 To date, most genetic studies in the athlete population have examined a subset of genes (out of more than 21,000 in the genome), using small sample sizes and qualitative measures of performance. To the best of our knowledge, there has not been a comprehensive genetic study of endurance athletes with strict quantitative eligibility criteria.2-4The ELITE project (Exercise at the Limit – Inherited Traits of Endurance) intends to investigate the world’s best endurance athletes, i.e. individuals with extremely high VO2max. A primary goal is to determine what role genetic variation plays in athletic ability. One of the ancillary goals of the project is to understand the unique genetic differences contributing to extreme fitness in women versus men. We will sequence and analyze the genomes of elite level competitive athletes from various countries (including USA, Scandinavia, UK, Japan, and Brazil) who are highly successful in one of several endurance sports (such as running, cross country skiing, triathlon, cycling, rowing). We have recruited 750 elite athletes (142 women and 608 men) who have been consented and undergone enhanced whole exome sequencing and/or MEGA chip GWAS analysis. Inclusion criteria for the study restricts to the highest tail end (>99.98th percentile or 1/5000), i.e. VO2max >63 ml/kg for women and >75 ml/kg for men. Even with differential eligibility, skewed recruitment (1:4) is a challenge.Our preliminary results show tantalizing evidence for potentially beneficial genetic variants in several highly plausible genes. Additionally, pilot burden testing on a subset of the athletes also showed promising results. While already promising, rigorous analysis, increased sample size and orthogonal replication is required as our next step. Mattsson CM, Wheeler M, Waggott D, Caleshu C, Ashley EA. Sports genetics moving forward - lessons learned from medical research. Physiol Genomics. 2016; 48(3):175-182.Bouchard C, Sarzynski MA, Rice TK, Kraus WE, Church TS, Sung YJ, Rao DC, Rankinen T. Genomic predictors of the maximal O₂ uptake response to standardized exercise training programs. J Appl Physiol (1985). 2011; 110(5):1160-70.Eynon N, Morán M, Birk R, Lucia A. The champions' mitochondria: is it genetically determined? A review on mitochondrial DNA and elite athletic performance. Physiol Genomics. 2011;43(13):789-98.Pitsiladis YP, Tanaka M, Eynon N, Bouchard C, North KN, Williams AG, Collins M, Moran CN, Britton SL, Fuku N, Ashley EA, Klissouras V, Lucia A, Ahmetov II, de Geus E, Alsayrafi M; Athlome Project Consortium. Athlome Project Consortium: a concerted effort to discover genomic and other "omic" markers of athletic performance. Physiol Genomics. 2016;48(3):183-90.
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| 12. |
- Moberg, Marcus, 1986-, et al.
(författare)
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Exercise Induces Different Molecular Responses in Trained and Untrained Human Muscle.
- 2020
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Ingår i: Medicine & Science in Sports & Exercise. - : Wolters Kluwer. - 0195-9131 .- 1530-0315. ; 52:8, s. 1679-1690
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Human skeletal muscle is thought to have heightened sensitivity to exercise stimulus when it has been previously trained (i.e., it possesses "muscle memory"). We investigated whether basal and acute resistance exercise-induced gene expression and cell signaling events are influenced by previous strength training history.METHODS: Accordingly, 19 training naïve women and men completed 10 weeks of unilateral leg strength training, followed by 20 weeks of detraining. Subsequently, an acute resistance exercise session was performed for both legs, with vastus lateralis biopsies taken at rest and 1 h after exercise in both legs (memory and control).RESULTS: The phosphorylation of AMPK and eEF2 was higher in the memory leg than in the control leg at both time points. Post-exercise phosphorylation of 4E-BP1 was higher in the memory leg than in the control leg. The memory leg had lower basal mRNA levels of total PGC1α, and, unlike the control leg, exhibited increases in PGC1α-ex1a transcripts after exercise. In the genes related to myogenesis (SETD3, MYOD1, and MYOG), mRNA levels differed between the memory and the untrained leg; these effects were evident primarily in the male subjects. Expression of the novel gene SPRYD7 was lower in the memory leg at rest and decreased after exercise only in the control leg, but SPRYD7 protein levels were higher in the memory leg.CONCLUSION: In conclusion, several key regulatory genes and proteins involved in muscular adaptations to resistance exercise are influenced by previous training history. Although the relevance and mechanistic explanation for these findings need further investigation, they support the view of a molecular muscle memory in response to training.
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| 13. |
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| 14. |
- Voisin, Sarah, et al.
(författare)
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An epigenetic clock for human skeletal muscle
- 2020
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Ingår i: Journal of Cachexia, Sarcopenia and Muscle. - : Wiley. - 2190-5991 .- 2190-6009. ; 11:4, s. 887-898
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ageing is associated with DNA methylation changes in all human tissues, and epigenetic markers can estimate chronological age based on DNA methylation patterns across tissues. However, the construction of the original pan‐tissue epigenetic clock did not include skeletal muscle samples and hence exhibited a strong deviation between DNA methylation and chronological age in this tissue.Methods: To address this, we developed a more accurate, muscle‐specific epigenetic clock based on the genome‐wide DNA methylation data of 682 skeletal muscle samples from 12 independent datasets (18–89 years old, 22% women, 99% Caucasian), all generated with Illumina HumanMethylation (HM) arrays (HM27, HM450, or HMEPIC). We also took advantage of the large number of samples to conduct an epigenome‐wide association study of age‐associated DNA methylation patterns in skeletal muscle.Results: The newly developed clock uses 200 cytosine‐phosphate–guanine dinucleotides to estimate chronological age in skeletal muscle, 16 of which are in common with the 353 cytosine‐phosphate–guanine dinucleotides of the pan‐tissue clock. The muscle clock outperformed the pan‐tissue clock, with a median error of only 4.6 years across datasets (vs. 13.1 years for the pan‐tissue clock, P < 0.0001) and an average correlation of ρ = 0.62 between actual and predicted age across datasets (vs. ρ = 0.51 for the pan‐tissue clock). Lastly, we identified 180 differentially methylated regions with age in skeletal muscle at a false discovery rate < 0.005. However, gene set enrichment analysis did not reveal any enrichment for gene ontologies.Conclusions: We have developed a muscle‐specific epigenetic clock that predicts age with better accuracy than the pan‐tissue clock. We implemented the muscle clock in an r package called Muscle Epigenetic Age Test available on Bioconductor to estimate epigenetic age in skeletal muscle samples. This clock may prove valuable in assessing the impact of environmental factors, such as exercise and diet, on muscle‐specific biological ageing processes.
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| 15. |
- Voisin, Sarah, et al.
(författare)
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Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle
- 2024
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Ingår i: Aging Cell. - 1474-9726. ; , s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates epigenetic aging in rodent muscle. Whether exercise training can decelerate, or reverse epigenetic aging in humans is unknown. Here, we performed a powerful meta-analysis of the methylome and transcriptome of an unprecedented number of human skeletal muscle samples (n = 3176). We show that: (1) individuals with higher baseline aerobic fitness have younger epigenetic and transcriptomic profiles, (2) exercise training leads to significant shifts of epigenetic and transcriptomic patterns toward a younger profile, and (3) muscle disuse "ages" the transcriptome. Higher fitness levels were associated with attenuated differential methylation and transcription during aging. Furthermore, both epigenetic and transcriptomic profiles shifted toward a younger state after exercise training interventions, while the transcriptome shifted toward an older state after forced muscle disuse. We demonstrate that exercise training targets many of the age-related transcripts and DNA methylation loci to maintain younger methylome and transcriptome profiles, specifically in genes related to muscle structure, metabolism, and mitochondrial function. Our comprehensive analysis will inform future studies aiming to identify the best combination of therapeutics and exercise regimes to optimize longevity.
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