Academic Journal
Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging
| العنوان: | Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging |
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| المؤلفون: | Jing, Ying, Zuo, Yuesheng, Yu, Yang, Sun, Liang, Yu, Zhengrong, Ma, Shuai, Zhao, Qian, Sun, Guoqiang, Hu, Huifang, Li, Jingyi, Huang, Daoyuan, Liu, Lixiao, Li, Jiaming, Xin, Zijuan, Huang, Haoyan, Izpisua Belmonte, Juan Carlos, Zhang, Weiqi, Wang, Si, Qu, Jing, Liu, Guang-Hui |
| المصدر: | Protein & Cell ; ISSN 1674-800X 1674-8018 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2022 |
| الوصف: | Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/procel/pwac061 |
| DOI: | 10.1093/procel/pwac061/47191760/pwac061.pdf |
| الاتاحة: | http://dx.doi.org/10.1093/procel/pwac061 https://academic.oup.com/proteincell/advance-article-pdf/doi/10.1093/procel/pwac061/47191760/pwac061.pdf |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.6F661C74 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/procel/pwac061 |
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