https://scholars.lib.ntu.edu.tw/handle/123456789/631365
標題: | Senomorphic effect of diphenyleneiodonium through AMPK/MFF/DRP1 mediated mitochondrial fission | 作者: | Liao, Keng-Mao Chen, Chih-Jung Luo, Wei-Jia Hsu, Chen-Wei SUNG-LIANG YU PAN-CHYR YANG KANG-YI SU |
關鍵字: | Anti-aging; Cellular senescence; DRP1; Diphenyleneiodonium; Mitochondrial fission; Senomorphic | 公開日期: | 六月-2023 | 出版社: | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER | 卷: | 162 | 來源出版物: | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie | 摘要: | With an aging population and the numerous health impacts associated with old age, the identification of anti-aging drugs has become an important new research direction. Although mitochondria have been recognized to affect aging, anti-aging drugs specifically targeting the mitochondria are less well characterized. In this study, diphenyleneiodonium (DPI) was identified as a potential senomorphic drug that functions by promoting mitochondrial fission. DPI significantly reduced the number of senescence-associated β-galactosidase (SA-β-gal) positive cells and increased the number of proliferating Ki-67 positive cells in BrdU or irradiation stress-induced senescent NIH3T3 cells or IMR90 cells and mouse embryonic fibroblasts (MEFs) replicative senescent cells. Cell cycle arrest genes and senescence-associated secretory phenotype (SASP) factors were downregulated with DPI treatment. In addition, the oxygen consumption rate (OCR) of mitochondrial respiration showed that DPI significantly reduced senescence-associated hyper OCR. Mechanistically, DPI promoted mitochondrial fission by enhancing AMPK/MFF phosphorylation and DRP1 mitochondrial translocation. Inhibition of DRP1 by Mdivi-1 abolished DPI-induced mitochondrial fission and the anti-senescence phenotype. Importantly, Eighty-eight-week-old mice treated with DPI had significantly reduced numbers of SA-β-gal positive cells and reduced expression of cell cycle arrest genes and SASP factors in their livers and kidneys. Pathological and functional assays showed DPI treatment not only reduced liver fibrosis and immune cell infiltration but also improved aged-related physical impairments in aged mice. Taken together, our study identified a potential anti-aging compound that exerts its effects through modulation of mitochondrial morphology. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/631365 | ISSN: | 0753-3322 | DOI: | 10.1016/j.biopha.2023.114616 |
顯示於: | 醫學檢驗暨生物技術學系 |
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