Research Paper Volume 12, Issue 16 pp 16111—16125

Testosterone ameliorates vascular aging via the Gas6/Axl signaling pathway

Yan-Qing Chen1,2, *, , Hui-Min Zhou1, *, , Fang-Fang Chen1, , Ya-Peng Liu1, , Lu Han1,3, , Ming Song1, , Zhi-Hao Wang1,4, , Wei Zhang1, , Yuan-Yuan Shang1, , Ming Zhong1, ,

  • 1 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China
  • 2 Department of Geriatrics, The Second Hospital of Shandong University, Jinan, Shandong China
  • 3 Department of General Practice, Qilu Hospital of Shandong University, Jinan, Shandong, China
  • 4 Department of Geriatric Medicine, Qilu Hospital of Shandong University, Key Laboratory of Cardiovascular Proteomics of Shandong Province, Jinan, Shandong, China
* Equal contribution

Received: November 16, 2019       Accepted: May 20, 2020       Published: July 27, 2020
How to Cite

Copyright © 2020 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.


GAS6: growth arrest-specific protein 6; WT: wild type; TU: testosterone undecanoate; SHBG: sex hormone binding globulin; VSMCs: vascular smooth muscle cells; IMT: intima-media thickness; Dd: diastolic diameter; Ds: systolic diameter; CD: coefficient distention; β: stiffness parameter; Ep: pressure-strain elastic modulus; DC: distensibility coefficient; CC: compliance coefficient; SBP: systolic blood pressure; DBP: diastolic blood pressure; MBP: mean blood pressure; PP: pulse pressure; TRT: testosterone replacement therapy; DOCA: deoxycorticosterone acetate; BCA: bicinchoninic acid assay; ECL: enhanced chemiluminescence; BSA: bovine serum albumin.