Functional effects of muscle PGC-1alpha in aged animals
Abstract PGC-1 (peroxisome-proliferator-activated receptor-γ coactivator-1) alpha is a potent transcriptional coactivator that coordinates the activation of numerous metabolic processes. Exercise strongly induces PGC-1alpha expression in muscle, and overexpression of PGC-1alpha in skeletal muscle ac...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-05-01
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| Series: | Skeletal Muscle |
| Online Access: | http://link.springer.com/article/10.1186/s13395-020-00231-8 |
| _version_ | 1811299507380420608 |
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| author | Steven Yang Emanuele Loro Shogo Wada Boa Kim Wei-Ju Tseng Kristina Li Tejvir S. Khurana Zoltan Arany |
| author_facet | Steven Yang Emanuele Loro Shogo Wada Boa Kim Wei-Ju Tseng Kristina Li Tejvir S. Khurana Zoltan Arany |
| author_sort | Steven Yang |
| collection | DOAJ |
| description | Abstract PGC-1 (peroxisome-proliferator-activated receptor-γ coactivator-1) alpha is a potent transcriptional coactivator that coordinates the activation of numerous metabolic processes. Exercise strongly induces PGC-1alpha expression in muscle, and overexpression of PGC-1alpha in skeletal muscle activates mitochondrial oxidative metabolism and neovascularization, leading to markedly increased endurance. In light of these findings, PGC-1alpha has been proposed to protect from age-associated sarcopenia, bone loss, and whole-body metabolic dysfunction, although these findings have been controversial. We therefore comprehensively evaluated muscle and whole-body function and metabolism in 24-month-old transgenic mice that over-express PGC-1alpha in skeletal muscle. We find that the powerful effects of PGC-1alpha on promoting muscle oxidative capacity and protection from muscle fatigability persist in aged animals, although at the expense of muscle strength. However, skeletal muscle PGC-1alpha does not prevent bone loss and in fact accentuates it, nor does it have long-term benefit on whole-body metabolic composition or insulin sensitivity. Protection from sarcopenia is seen in male animals with overexpression of PGC-1alpha in skeletal muscle but not in female animals. In summary, muscle-specific expression of PGC-1alpha into old age has beneficial effects on muscle fatigability and may protect from sarcopenia in males, but does not improve whole-body metabolism and appears to worsen age-related trabecular bone loss. |
| first_indexed | 2024-04-13T06:36:50Z |
| format | Article |
| id | doaj.art-bb4134d271df46789a140a70766d5d36 |
| institution | Directory Open Access Journal |
| issn | 2044-5040 |
| language | English |
| last_indexed | 2024-04-13T06:36:50Z |
| publishDate | 2020-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Skeletal Muscle |
| spelling | doaj.art-bb4134d271df46789a140a70766d5d362022-12-22T02:57:54ZengBMCSkeletal Muscle2044-50402020-05-011011810.1186/s13395-020-00231-8Functional effects of muscle PGC-1alpha in aged animalsSteven Yang0Emanuele Loro1Shogo Wada2Boa Kim3Wei-Ju Tseng4Kristina Li5Tejvir S. Khurana6Zoltan Arany7Department of Medicine, Perelman School of Medicine, University of PennsylvaniaDepartment of Physiology and Pennsylvania Muscle Institute, Perelman School of Medicine, University of PennsylvaniaDepartment of Medicine, Perelman School of Medicine, University of PennsylvaniaDepartment of Medicine, Perelman School of Medicine, University of PennsylvaniaDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of PennsylvaniaDepartment of Medicine, Perelman School of Medicine, University of PennsylvaniaDepartment of Physiology and Pennsylvania Muscle Institute, Perelman School of Medicine, University of PennsylvaniaDepartment of Medicine, Perelman School of Medicine, University of PennsylvaniaAbstract PGC-1 (peroxisome-proliferator-activated receptor-γ coactivator-1) alpha is a potent transcriptional coactivator that coordinates the activation of numerous metabolic processes. Exercise strongly induces PGC-1alpha expression in muscle, and overexpression of PGC-1alpha in skeletal muscle activates mitochondrial oxidative metabolism and neovascularization, leading to markedly increased endurance. In light of these findings, PGC-1alpha has been proposed to protect from age-associated sarcopenia, bone loss, and whole-body metabolic dysfunction, although these findings have been controversial. We therefore comprehensively evaluated muscle and whole-body function and metabolism in 24-month-old transgenic mice that over-express PGC-1alpha in skeletal muscle. We find that the powerful effects of PGC-1alpha on promoting muscle oxidative capacity and protection from muscle fatigability persist in aged animals, although at the expense of muscle strength. However, skeletal muscle PGC-1alpha does not prevent bone loss and in fact accentuates it, nor does it have long-term benefit on whole-body metabolic composition or insulin sensitivity. Protection from sarcopenia is seen in male animals with overexpression of PGC-1alpha in skeletal muscle but not in female animals. In summary, muscle-specific expression of PGC-1alpha into old age has beneficial effects on muscle fatigability and may protect from sarcopenia in males, but does not improve whole-body metabolism and appears to worsen age-related trabecular bone loss.http://link.springer.com/article/10.1186/s13395-020-00231-8 |
| spellingShingle | Steven Yang Emanuele Loro Shogo Wada Boa Kim Wei-Ju Tseng Kristina Li Tejvir S. Khurana Zoltan Arany Functional effects of muscle PGC-1alpha in aged animals Skeletal Muscle |
| title | Functional effects of muscle PGC-1alpha in aged animals |
| title_full | Functional effects of muscle PGC-1alpha in aged animals |
| title_fullStr | Functional effects of muscle PGC-1alpha in aged animals |
| title_full_unstemmed | Functional effects of muscle PGC-1alpha in aged animals |
| title_short | Functional effects of muscle PGC-1alpha in aged animals |
| title_sort | functional effects of muscle pgc 1alpha in aged animals |
| url | http://link.springer.com/article/10.1186/s13395-020-00231-8 |
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