Testosterone ameliorates vascular aging via the Gas6/Axl signaling pathway
| Autor: | Ming Song, Lu Han, Wei Zhang, Ya-Peng Liu, Ming Zhong, Hui-Min Zhou, Zhi-Hao Wang, Yan-qing Chen, Yuan-yuan Shang, Fang-Fang Chen |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
Senescence Aging medicine.medical_specialty Cell Vascular Remodeling Vascular Stiffness Proto-Oncogene Proteins Gas6 Internal medicine medicine Animals Arterial Pressure Testosterone Phosphorylation Protein kinase B Aorta Cellular Senescence Mice Knockout Forkhead Box Protein O1 GAS6 business.industry Age Factors Wild type Receptor Protein-Tyrosine Kinases Axl Cell Biology Fibrosis Axl Receptor Tyrosine Kinase Carotid Arteries medicine.anatomical_structure Endocrinology vascular aging Intercellular Signaling Peptides and Proteins vascular stiffening Signal transduction business Proto-Oncogene Proteins c-akt Signal Transduction Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| DOI: | 10.18632/aging.103584 |
| Popis: | Low serum testosterone level is associated with aging-related vascular stiffness, but the underlying mechanism is unclear. The Growth arrest-specific protein 6 (Gas6) /Axl pathway has been proved to play important roles in cell senescence. In this study, we intend to explore whether Gas6/Axl is involved in the effect of testosterone on vascular aging amelioration. Vascular aging models of wild type and Axl-/- mice were established by natural aging. Mice of these two gene types were randomized into young group, aging group and testosterone undecanoate (TU) treatment group. Mice were treated with TU (37.9 mg/kg) in the TU group, which treated with solvent reagent served as control. The aging mice exhibited decreases in serum testosterone, Gas6 and Axl levels and an increase in cell senescence, manifested age-related vascular remodeling. Testosterone treatment induced testosterone and Gas6 levels in serum, and ameliorated cell senescence and vascular remodeling in aging mice. Furthermore, we uncover the underlying molecular mechanism and show that testosterone treatment restored the phosphorylation of Akt and FoxO1a. Axl knockout accelerated cell senescence and vascular remodeling, and resisted the anti-aging effect of testosterone. Testosterone might exert a protective effect on vascular aging by improving cell senescence and vascular remodeling through the Gas6/Axl pathway. |
| Databáze: | OpenAIRE |
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