| 1. |
|
|
| 2. |
- Voisin, Sarah, et al.
(författare)
-
Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle
- 2024
-
Ingår i: Aging Cell. - 1474-9726. ; , s. 1-15
-
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.
|
|
| 3. |
- Chapman, Mark A., et al.
(författare)
-
Skeletal Muscle Transcriptomic Comparison between Long-Term Trained and Untrained Men and Women
- 2020
-
Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 31:12
-
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.
|
|
| 4. |
- Emanuelsson, Eric B., et al.
(författare)
-
Remodeling of the human skeletal muscle proteome found after long-term endurance training but not after strength training
- 2024
-
Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 27:1
-
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.
|
|
| 5. |
|
|
| 6. |
- Lindholm, Malene E., et al.
(författare)
-
The human skeletal muscle transcriptome : sex differences, alternative splicing, and tissue homogeneity assessed with RNA sequencing
- 2014
-
Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 211, s. 38-38
-
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.
|
|
| 7. |
- Lindholm, Malene E., et al.
(författare)
-
The Impact of Endurance Training on Human Skeletal Muscle Memory, Global Isoform Expression and Novel Transcripts
- 2016
-
Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 12:9
-
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.
|
|
| 8. |
- Moberg, Marcus, 1986-, et al.
(författare)
-
Exercise Induces Different Molecular Responses in Trained and Untrained Human Muscle.
- 2020
-
Ingår i: Medicine & Science in Sports & Exercise. - : Wolters Kluwer. - 0195-9131 .- 1530-0315. ; 52:8, s. 1679-1690
-
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.
|
|
| 9. |
- Voisin, Sarah, et al.
(författare)
-
An epigenetic clock for human skeletal muscle
- 2020
-
Ingår i: Journal of Cachexia, Sarcopenia and Muscle. - : Wiley. - 2190-5991 .- 2190-6009. ; 11:4, s. 887-898
-
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.
|
|
