Cheng Yanfei, Zheng Guobin, Huang Heming, Ni Jingyu, Zhao Yun, Sun Yuting, Chang Yingxin, Liu Shangjing, He Feng, Li Dan, Guo Yuying, Miao Yaodong, Xu Mengxin, Wang Dongyue, Zhang Yunsha, Hua Yunqing, Yang Shu, Fan Guanwei, Ma Chuanrui
First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin 300134, China.
Theranostics. 2025 Mar 18;15(10):4345-4367. doi: 10.7150/thno.110324. eCollection 2025.
Vascular aging is a prior marker of human aging and a significant contributor to atherosclerosis and vascular calcification. However, there are limited pharmacological options available to mitigate vascular aging. Thus, understanding the mechanisms underlying vascular aging and age-related atherosclerosis and vascular calcification is crucial. This study investigates the targets of vascular aging and elucidates the role and mechanisms of spore powder (GLSP) in mitigating vascular aging and aging-associated atherosclerosis as well as vascular calcification. The anti-vascular aging effects of GLSP was determined in aged C57BL/6J mice and the targets of GLSP was identified through transcriptome sequencing. Additionally, the protective effects of GLSP on the aged vasculature were assessed by examining atherosclerosis in apoE mice and vascular calcification in VD and nicotine-induced mice. , the protective effects of GLSP triterpenes against vascular aging and calcification was determined in vascular smooth muscle cells (VSMCs). GLSP exerted anti-vascular aging effects by regulating the cell cycle and senescence-associated secretory phenotype (SASP), mitigating DNA damage, reducing oxidative stress, improving mitochondrial function and modulating metabolic levels. Furthermore, GLSP improved vascular aging-associated atherosclerosis and vascular calcification . Mechanistically, RNA sequencing revealed an upregulation of Sirt7 expression after GLSP treatment. Sirt7 inhibitor exacerbated VSMCs senescence and calcification in senescent VSMCs and abolished the anti-senescence and the inhibitory effect of GLSP triterpenes on VSMCs senescence and calcification. Innovatively, we found that Sirt7 interacted with Keap1 and facilitated Keap1 deacetylation, which promoted Keap1-Nrf2 dissociation and consequently enhanced Nrf2 nuclear translocation and activation. GLSP alleviates vascular aging by exerting antioxidant effects through the activation of the Sirt7-Nrf2 axis, providing a promising new strategy for delaying vascular aging, atherosclerosis and vascular calcification.
血管老化是人类衰老的一个前期标志，也是动脉粥样硬化和血管钙化的一个重要促成因素。然而，目前用于减轻血管老化的药物选择有限。因此，了解血管老化以及与年龄相关的动脉粥样硬化和血管钙化的潜在机制至关重要。本研究调查了血管老化的靶点，并阐明了灵芝孢子粉（GLSP）在减轻血管老化、与衰老相关的动脉粥样硬化以及血管钙化方面的作用和机制。在老年C57BL/6J小鼠中测定了GLSP的抗血管老化作用，并通过转录组测序确定了GLSP的靶点。此外，通过检测载脂蛋白E小鼠的动脉粥样硬化以及维生素D和尼古丁诱导小鼠的血管钙化，评估了GLSP对衰老血管系统的保护作用。在血管平滑肌细胞（VSMC）中测定了GLSP三萜对血管老化和钙化的保护作用。GLSP通过调节细胞周期和衰老相关分泌表型（SASP）、减轻DNA损伤、降低氧化应激、改善线粒体功能和调节代谢水平发挥抗血管老化作用。此外，GLSP改善了与血管老化相关的动脉粥样硬化和血管钙化。从机制上讲，RNA测序显示GLSP处理后Sirt7表达上调。Sirt7抑制剂加剧了衰老VSMC中的VSMC衰老和钙化，并消除了GLSP三萜对VSMC衰老和钙化的抗衰老及抑制作用。创新性地，我们发现Sirt7与Keap1相互作用并促进Keap1去乙酰化，这促进了Keap1-Nrf2解离，从而增强了Nrf2核转位和激活。GLSP通过激活Sirt7-Nrf2轴发挥抗氧化作用来减轻血管老化，为延缓血管老化、动脉粥样硬化和血管钙化提供了一种有前景的新策略。
