دورية أكاديمية
Insulin-Like Growth Factor I Prevents Cellular Aging via Activation of Mitophagy
| العنوان: | Insulin-Like Growth Factor I Prevents Cellular Aging via Activation of Mitophagy |
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| المؤلفون: | Xuwei Hou, Zhaohui Li, Yusuke Higashi, Patrice Delafontaine, Sergiy Sukhanov |
| المصدر: | Journal of Aging Research, Vol 2020 (2020) |
| بيانات النشر: | Hindawi Limited, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Geriatrics |
| مصطلحات موضوعية: | Geriatrics, RC952-954.6 |
| الوصف: | Mitochondrial dysfunction is a hallmark of cellular aging. Mitophagy is a critical mitochondrial quality control mechanism that removes dysfunctional mitochondria and contributes to cell survival. Insulin-like growth factor 1 (IGF-1) promotes survival of smooth muscle cells (SMCs), but its potential effect on cellular aging is unknown yet. We found that IGF-1 decreased cell senescence, prevented DNA telomere shortening, increased mitochondrial membrane potential, activated cytochrome C oxidase, and reduced mitochondrial DNA damage in long-term cultured (aged) aortic SMC, suggesting an antiaging effect. IGF-1 increased mitophagy in aged cells, and this was associated with decreased expression of cyclin-dependent kinase inhibitors p16 and p21 and elevated levels of Nrf2 and Sirt3, regulators of mitophagy and mitochondrial biogenesis. SiRNA-induced inhibition of either Nrf2 or Sirt3 blocked IGF-1-induced upregulation of mitophagy, suggesting that the Nrf2/Sirt3 pathway was required for IGF-1’s effect on mitophagy. PINK1 is a master regulator of mitophagy. PINK1 silencing suppressed mitophagy and inhibited IGF-1-induced antiaging effects in aged SMC, consistent with an essential role of mitophagy in IGF-1’s effect on cellular aging. Thus, IGF-1 inhibited cellular aging via Nrf2/Sirt3-dependent activation of mitophagy. Our data suggest that activation of IGF-1 signaling is a novel potential strategy to activate mitophagy and slow cellular aging. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2090-2204 2090-2212 |
| Relation: | https://doaj.org/toc/2090-2204; https://doaj.org/toc/2090-2212 |
| DOI: | 10.1155/2020/4939310 |
| URL الوصول: | https://doaj.org/article/c1d1a32b4b9c4b5fa6681e35c39a3913 |
| رقم الأكسشن: | edsdoj.1d1a32b4b9c4b5fa6681e35c39a3913 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20902204 20902212 |
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| DOI: | 10.1155/2020/4939310 |