Department of Physical Education, Yonsei University, Seoul, South Korea.
Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea.
Exp Gerontol. 2019 Jan;115:148-154. doi: 10.1016/j.exger.2018.08.009. Epub 2018 Sep 4.
Excessive oxidative stress leads to aging due to persistent damage to the cells, tissues, and the entire organism. Immunosenescence is also a devastating consequence of oxidative stress, but there is a lack of research on effective ways to overcome it. In this study, we used physiologic and immunological aging mouse models that had sustained oxidative stress to investigate whether voluntary exercise and/or antioxidant treatment could overcome oxidative damage as well as aging. We established an aging model induced by continuously administering d-galactose (d-gal) to 6-week-old female C57BL/6J mice. We also assessed reversal of immunosenescence by providing free-wheel running and vitamin E (vit E) supplementation to this aging model. As an aging index, the level of advanced glycation end products (AGEs) in the blood was measured. Phenotypes of T cells in the thymus and spleen were examined as an index of immunosenescence. Intracellular reactive oxygen species (ROS) levels in the mouse spleen and levels of AGEs in the blood were significantly higher after 6 weeks of d-gal administration. In addition, immunosenescence was observed, in which the naïve:effector cell ratio in the spleen decreased. After 4 weeks of free-wheel running and vit E administration, both intracellular ROS and serum AGE levels decreased. Above all, free-wheel running restored the naïve:effector ratio of cytotoxic T lymphocytes reduced by d-gal administration. Taken together, these results suggest that voluntary exercise may be effective in restoring immunosenescence induced by oxidative stress.
过度的氧化应激会导致细胞、组织和整个机体的持续损伤，从而导致衰老。免疫衰老也是氧化应激的一个毁灭性后果，但目前缺乏克服氧化应激的有效方法的研究。在这项研究中，我们使用了持续氧化应激的生理性和免疫性衰老小鼠模型，来研究自愿运动和/或抗氧化治疗是否可以克服氧化损伤和衰老。我们建立了一个通过连续给予 6 周龄雌性 C57BL/6J 小鼠 D-半乳糖（D-gal）来诱导衰老的模型。我们还通过为该衰老模型提供自由轮跑和维生素 E（vit E）补充，评估了免疫衰老的逆转。作为衰老的指标，我们测量了血液中晚期糖基化终产物（AGEs）的水平。胸腺和脾脏 T 细胞的表型被作为免疫衰老的指标进行了检查。在 D-gal 给药 6 周后，小鼠脾脏内细胞内活性氧（ROS）水平和血液中的 AGEs 水平显著升高。此外，观察到了免疫衰老，其中脾脏中幼稚：效应细胞比降低。在自由轮跑和 vit E 给药 4 周后，细胞内 ROS 和血清 AGE 水平均降低。最重要的是，自由轮跑恢复了 D-gal 给药导致的细胞毒性 T 淋巴细胞幼稚：效应比的降低。综上所述，这些结果表明，自愿运动可能有助于恢复氧化应激引起的免疫衰老。
