Individual transcriptomic response to strength training for patients with myotonic dystrophy type 1
Myotonic dystrophy type 1 (DM1), the most common form of adult-onset muscular dystrophy, is caused by a CTG expansion resulting in significant transcriptomic dysregulation that leads to muscle weakness and wasting. While strength training is clinically beneficial in DM1, molecular effects had not be...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2023-07-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.163856 |
| _version_ | 1797634327079550976 |
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| author | Emily E. Davey Cécilia Légaré Lori Planco Sharon Shaughnessy Claudia D. Lennon Marie-Pier Roussel Hannah K. Shorrock Man Hung John Douglas Cleary Elise Duchesne J. Andrew Berglund |
| author_facet | Emily E. Davey Cécilia Légaré Lori Planco Sharon Shaughnessy Claudia D. Lennon Marie-Pier Roussel Hannah K. Shorrock Man Hung John Douglas Cleary Elise Duchesne J. Andrew Berglund |
| author_sort | Emily E. Davey |
| collection | DOAJ |
| description | Myotonic dystrophy type 1 (DM1), the most common form of adult-onset muscular dystrophy, is caused by a CTG expansion resulting in significant transcriptomic dysregulation that leads to muscle weakness and wasting. While strength training is clinically beneficial in DM1, molecular effects had not been studied. To determine whether training rescued transcriptomic defects, RNA-Seq was performed on vastus lateralis samples from 9 male patients with DM1 before and after a 12-week strength-training program and 6 male controls who did not undergo training. Differential gene expression and alternative splicing analysis were correlated with the one-repetition maximum strength evaluation method (leg extension, leg press, hip abduction, and squat). While training program–induced improvements in splicing were similar among most individuals, rescued splicing events varied considerably between individuals. Gene expression improvements were highly varied between individuals, and the percentage of differentially expressed genes rescued after training were strongly correlated with strength improvements. Evaluating transcriptome changes individually revealed responses to the training not evident from grouped analysis, likely due to disease heterogeneity and individual exercise response differences. Our analyses indicate that transcriptomic changes are associated with clinical outcomes in patients with DM1 undergoing training and that these changes are often specific to the individual and should be analyzed accordingly. |
| first_indexed | 2024-03-11T12:06:05Z |
| format | Article |
| id | doaj.art-d641442504a74f18b3344b7cb793d359 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:06:05Z |
| publishDate | 2023-07-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-d641442504a74f18b3344b7cb793d3592023-11-07T16:25:54ZengAmerican Society for Clinical investigationJCI Insight2379-37082023-07-01814Individual transcriptomic response to strength training for patients with myotonic dystrophy type 1Emily E. DaveyCécilia LégaréLori PlancoSharon ShaughnessyClaudia D. LennonMarie-Pier RousselHannah K. ShorrockMan HungJohn Douglas ClearyElise DuchesneJ. Andrew BerglundMyotonic dystrophy type 1 (DM1), the most common form of adult-onset muscular dystrophy, is caused by a CTG expansion resulting in significant transcriptomic dysregulation that leads to muscle weakness and wasting. While strength training is clinically beneficial in DM1, molecular effects had not been studied. To determine whether training rescued transcriptomic defects, RNA-Seq was performed on vastus lateralis samples from 9 male patients with DM1 before and after a 12-week strength-training program and 6 male controls who did not undergo training. Differential gene expression and alternative splicing analysis were correlated with the one-repetition maximum strength evaluation method (leg extension, leg press, hip abduction, and squat). While training program–induced improvements in splicing were similar among most individuals, rescued splicing events varied considerably between individuals. Gene expression improvements were highly varied between individuals, and the percentage of differentially expressed genes rescued after training were strongly correlated with strength improvements. Evaluating transcriptome changes individually revealed responses to the training not evident from grouped analysis, likely due to disease heterogeneity and individual exercise response differences. Our analyses indicate that transcriptomic changes are associated with clinical outcomes in patients with DM1 undergoing training and that these changes are often specific to the individual and should be analyzed accordingly.https://doi.org/10.1172/jci.insight.163856Muscle biologyTherapeutics |
| spellingShingle | Emily E. Davey Cécilia Légaré Lori Planco Sharon Shaughnessy Claudia D. Lennon Marie-Pier Roussel Hannah K. Shorrock Man Hung John Douglas Cleary Elise Duchesne J. Andrew Berglund Individual transcriptomic response to strength training for patients with myotonic dystrophy type 1 JCI Insight Muscle biology Therapeutics |
| title | Individual transcriptomic response to strength training for patients with myotonic dystrophy type 1 |
| title_full | Individual transcriptomic response to strength training for patients with myotonic dystrophy type 1 |
| title_fullStr | Individual transcriptomic response to strength training for patients with myotonic dystrophy type 1 |
| title_full_unstemmed | Individual transcriptomic response to strength training for patients with myotonic dystrophy type 1 |
| title_short | Individual transcriptomic response to strength training for patients with myotonic dystrophy type 1 |
| title_sort | individual transcriptomic response to strength training for patients with myotonic dystrophy type 1 |
| topic | Muscle biology Therapeutics |
| url | https://doi.org/10.1172/jci.insight.163856 |
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