A new Drosophila model of prolonged inactivity shortens lifespan and impairs muscle function
Abstract Prolonged inactivity due to medical conditions can cause chronic muscle disuse and lead to physical incapacity and poor quality of life. Here, we developed a Drosophila model of confinement inactivity (CI) to observe its effects on lifespan and muscle function. We found that, similar to mam...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-13446-w |
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| author | Jodi Protasiewicz Sarah Snider Mousumee Khan Li Tao Robert J. Wessells Alyson Sujkowski |
| author_facet | Jodi Protasiewicz Sarah Snider Mousumee Khan Li Tao Robert J. Wessells Alyson Sujkowski |
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| description | Abstract Prolonged inactivity due to medical conditions can cause chronic muscle disuse and lead to physical incapacity and poor quality of life. Here, we developed a Drosophila model of confinement inactivity (CI) to observe its effects on lifespan and muscle function. We found that, similar to mammalian models and humans, CI negatively impacted longevity and function in Drosophila. Confined flies had impaired mobility, shorter lifespan, and reduced muscle integrity compared to their freely mobile siblings. These findings establish a new, highly efficient platform for studying long term effects of chronic sedentary behavior and muscle disuse in the genetically tractable Drosophila model. In addition, we found that temporarily removing flies from CI for scheduled bouts of forced physical exercise ameliorated negative effects, in part by improving muscle homeostasis. Finally, we tested whether muscle overexpression of 3 exercise-responsive genes, dPGC-1α, dFNDC5, or dSesn, could prevent the negative impact of CI on fly aging, even without physical exercise. We previously established that overexpression of these factors phenocopies exercise effects in aging wild-type and disease model flies. We found that when overexpressed in muscle, dSesn prevented premature declines in endurance, and dFNDC5 protected speed and endurance. This new model can be used in the future for mechanistic studies to identify preventative and therapeutic targets for diseases associated with chronic inactivity. |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-0bd3acc9d4db4e6aa88aebee2393fe7c2025-08-20T03:42:25ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-13446-wA new Drosophila model of prolonged inactivity shortens lifespan and impairs muscle functionJodi Protasiewicz0Sarah Snider1Mousumee Khan2Li Tao3Robert J. Wessells4Alyson Sujkowski5Department of Pharmacology, Wayne State University School of MedicineDepartment of Pharmacology, Wayne State University School of MedicineDepartment of Physiology, Wayne State University School of MedicineDepartment of Physiology, Wayne State University School of MedicineDepartment of Physiology, Wayne State University School of MedicineDepartment of Pharmacology, Wayne State University School of MedicineAbstract Prolonged inactivity due to medical conditions can cause chronic muscle disuse and lead to physical incapacity and poor quality of life. Here, we developed a Drosophila model of confinement inactivity (CI) to observe its effects on lifespan and muscle function. We found that, similar to mammalian models and humans, CI negatively impacted longevity and function in Drosophila. Confined flies had impaired mobility, shorter lifespan, and reduced muscle integrity compared to their freely mobile siblings. These findings establish a new, highly efficient platform for studying long term effects of chronic sedentary behavior and muscle disuse in the genetically tractable Drosophila model. In addition, we found that temporarily removing flies from CI for scheduled bouts of forced physical exercise ameliorated negative effects, in part by improving muscle homeostasis. Finally, we tested whether muscle overexpression of 3 exercise-responsive genes, dPGC-1α, dFNDC5, or dSesn, could prevent the negative impact of CI on fly aging, even without physical exercise. We previously established that overexpression of these factors phenocopies exercise effects in aging wild-type and disease model flies. We found that when overexpressed in muscle, dSesn prevented premature declines in endurance, and dFNDC5 protected speed and endurance. This new model can be used in the future for mechanistic studies to identify preventative and therapeutic targets for diseases associated with chronic inactivity.https://doi.org/10.1038/s41598-025-13446-wProlonged inactivityConfinementExerciseDrosophila melanogaster |
| spellingShingle | Jodi Protasiewicz Sarah Snider Mousumee Khan Li Tao Robert J. Wessells Alyson Sujkowski A new Drosophila model of prolonged inactivity shortens lifespan and impairs muscle function Scientific Reports Prolonged inactivity Confinement Exercise Drosophila melanogaster |
| title | A new Drosophila model of prolonged inactivity shortens lifespan and impairs muscle function |
| title_full | A new Drosophila model of prolonged inactivity shortens lifespan and impairs muscle function |
| title_fullStr | A new Drosophila model of prolonged inactivity shortens lifespan and impairs muscle function |
| title_full_unstemmed | A new Drosophila model of prolonged inactivity shortens lifespan and impairs muscle function |
| title_short | A new Drosophila model of prolonged inactivity shortens lifespan and impairs muscle function |
| title_sort | new drosophila model of prolonged inactivity shortens lifespan and impairs muscle function |
| topic | Prolonged inactivity Confinement Exercise Drosophila melanogaster |
| url | https://doi.org/10.1038/s41598-025-13446-w |
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