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from: tainan
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from: taoyuan
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from: Kaohsiung
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from: hongkong
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from: yunlin
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from: Kaohsiung
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from: taizhong
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Dr. Song
from: Kaohsiung
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| 2023-11-15 13:17:51 | onclick： | Research on mechanisms of occurrence gives hope for delaying aging |
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Recently, Zhao Yuzheng, a professor at East China University of Technology, and Sun Yu, a researcher at the Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, published a paper in Nature-Metabolism.
It is one of the important goals of biomedical research to reveal the mechanism of senescence from molecular and cell level and find therapeutic targets to delay senescence.In this study, the expression characteristics and metabolic activity of senescent cells were analyzed, and the metabolic regulatory enzyme PDK4 was significantly increased during senescent cells.More importantly, the expression level of PDK4 in the focal tissue of cancer patients was positively correlated with cell aging at microenvironmental level and negatively correlated with survival period.
The research team demonstrated that glycolysis and tricarboxylic acid cycle metabolism of senescent cells were significantly enhanced, especially lactic acid production.Further studies have shown that lactic acid in prostate cancer microenvironment can induce tumor cell proliferation, migration and invasion.
The combination of PDK4 specific inhibitors and chemotherapy drugs reduced tumor volume by 75%, and did not cause severe systemic cytotoxic effects.Histological analysis showed that PDK4 inhibitors could block cell senescence in tumor microenvironment.
In view of the important role of PDK4 in cell aging, this study also explored the role of PDK4-mediated lactate metabolism in aging-related chronic lesions.In wild mice aged 20 months, placebo or inhibitor intervention was performed. After 4 months, specific inhibitors partially reversed the aging of liver, lung, prostate and myocardial tissues such as alveolar dilatation, liver dysfunction, etc.In addition, PDK4-targeted life expectancy was increased by 4.2%, while overall risk of death was reduced by 53.4%.Therefore, this study illustrates the deep relationship between metabolic reprogramming and aging pathology, including cancer, as well as decreased respiratory, motor, and liver functions from a molecular and cellular perspective.
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