《生命科学》 2026, 38(6): 1017-1027
空间微重力下血管衰老的力学解码与干预展望
摘 要：
航天微重力环境下，血管受到的剪切应力、周期性牵拉、静水压力均发生显著变化，这些力学变化是导致航天员心血管功能失调的重要原因。本文综述了长期航天飞行对血管结构和功能的影响及其力学生物学最新进展，提示了力学因素在血管衰老进程中的关键作用，并对其临床应用和干预策略进行了讨论和展望，旨在为我国航天员长期在轨健康保护及老年血管疾病防治提供新靶点和新策略。
通讯作者：李 嘉 , Email:jiali816@fmmu.edu.cn
Abstract:
With the advancement of long-duration space missions including lunar and Martian explorations, elucidating the mechanisms underlying microgravity-induced vascular aging-like changes is crucial for safeguarding astronaut health and providing insights into the management of terrestrial age-related vascular diseases. This review synthesizes evidence regarding the characteristics, mechano-biological pathways, and clinical implications of accelerated vascular aging associated with long-term spaceflight, aiming to identify novel therapeutic targets for both astronaut health protection and ground-based clinical practice. The core trigger of microgravity-related vascular perturbations is the ″cephalad fluid shift″, which refers to the translocation of approximately 2 L of fluid from the lower to the upper body and drastically alters key biomechanical forces—shear stress, cyclic mechanical stretch, and hydrostatic pressure—acting on blood vessels. Clinical data demonstrate that 6-month spaceflight induces vascular aging equivalent to 10~20 years on Earth, characterized by increased carotid intima-media thickness, decreased vascular compliance, accelerated pulse wave velocity, and jugular venous blood flow stasis in 55% of International Space Station astronauts. Animal and in vitro models have confirmed vascular stiffening, fibrosis, and elevated senescence-associated markers. Vascular endothelial cells lose spindle-shaped alignment, develop organelle damage, exhibit reduced nitric oxide synthesis and disrupted tight junctions; vascular smooth muscle cells (VSMCs) transdifferentiate from contractile to synthetic phenotypes with downregulated α-smooth muscle actin (α-SMA) and upregulated osteopontin (OPN), accompanied by abnormal extracellular matrix deposition. Mechanistically, biomechanical alterations are sensed by Piezo1 channels, G protein-coupled receptors (GPCRs), and integrins, which activate downstream signaling cascades. Shear stress redistribution, with increased time-averaged wall shear stress (TAWSS) in the upper body and decreased TAWSS in the lower body, induces cytoskeletal remodeling of vascular endothelial cells, inhibits endothelial nitric oxide synthase (eNOS) activity, and activates nuclear factor-κB (NF-κB), thereby promoting inflammatory responses. Elevated cyclic stretch drives VSMCs phenotypic switching through the RhoA/ROCK and YAP/TAZ signaling pathways. Loss of hydrostatic pressure gradients impairs vascular permeability via Piezo1-dependent mechanisms. Microgravity also directly induces oxidative stress characterized by excessive mitochondrial reactive oxygen species (ROS) production, cell cycle arrest associated with dysregulated Cyclin B1 and the p53-p21 pathway, cytoskeletal reorganization, and persistent epigenetic modifications, which further exacerbate cellular senescence. Sex-specific hemodynamic differences such as a more pronounced reduction in lower limb shear stress in males add additional complexity to these pathological processes. Current challenges include inadequate ground-based simulation models, small sample sizes, insufficient data on female astronauts, and underdeveloped real-time in-flight monitoring technologies. Proposed strategies include: (1) multimodal monitoring integrated portable ultrasound and biosensors with artificial intelligence (AI) for early warning of vascular dysfunction; (2) personalized interventions including ″exercise-mimetic pills″ leveraging multi-omics technologies and digital twin models; (3) strengthened interdisciplinary collaboration and international sharing of spaceflight-related data. This review highlights the dysregulation of mechano-biological signaling as the central driver of microgravity-induced vascular aging. Space-based research provides valuable insights into the pathogenesis of terrestrial vascular diseases such as hypertensive vascular injury and atherosclerosis, with mechanosensitive pathways including Piezo1 and YAP/TAZ emerging as promising therapeutic targets. Future research should prioritize longitudinal follow-up of astronauts and the refinement of ground-based simulation models to ensure the safety of long-duration space missions and advance global vascular healthcare.
Communication Author：LI Jia , Email:jiali816@fmmu.edu.cn
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