Cristobal F. Rivera, Yasmeen M. Farra, Michele Silvestro, Steven Medvedovsky, Jacqueline Matz, Muhammad Yogi Pratama, John Vlahos, Bhama Ramkhelawon, Chiara Bellini
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引用次数: 0
摘要
主动脉僵化是慢性衰老的一种不可避免的表现形式,然而沿主动脉长度方向和通过主动脉壁协调区域和层特异性适应的机械分子程序尚未完全确定。在这里,我们发现升主动脉(ATA)与主动脉远端相比,被动循环伸缩性的下降更为明显,而且在衰老过程中,升主动脉内侧和外侧的胶原蛋白含量都会增加。与年轻样本相比,老年主动脉瘤组织的单细胞 RNA 测序显示了细胞衰老、重塑和炎症反应的改变,同时伴随着 T 淋巴细胞的富集和血管平滑肌细胞的稀少。T 淋巴细胞集群聚集在血管前壁,而机械敏感性 Piezo-1 的激活增强了血管收缩,导致 ATA 组织整体功能下降。这些结果将 ATA 的免疫-机械老化过程描绘成一个最终导致管道变硬的过程,而管道变硬会导致多种致病信号的累积,进而引发疾病。
Mapping the unicellular transcriptome of the ascending thoracic aorta to changes in mechanosensing and mechanoadaptation during aging
Aortic stiffening is an inevitable manifestation of chronological aging, yet the mechano-molecular programs that orchestrate region- and layer-specific adaptations along the length and through the wall of the aorta are incompletely defined. Here, we show that the decline in passive cyclic distensibility is more pronounced in the ascending thoracic aorta (ATA) compared to distal segments of the aorta and that collagen content increases in both the medial and adventitial compartments of the ATA during aging. The single-cell RNA sequencing of aged ATA tissues reveals altered cellular senescence, remodeling, and inflammatory responses accompanied by enrichment of T-lymphocytes and rarefaction of vascular smooth muscle cells, compared to young samples. T lymphocyte clusters accumulate in the adventitia, while the activation of mechanosensitive Piezo-1 enhances vasoconstriction and contributes to the overall functional decline of ATA tissues. These results portray the immuno-mechanical aging of the ATA as a process that culminates in a stiffer conduit permissive to the accrual of multi-gerogenic signals priming to disease development.
期刊介绍:
Aging Cell, an Open Access journal, delves into fundamental aspects of aging biology. It comprehensively explores geroscience, emphasizing research on the mechanisms underlying the aging process and the connections between aging and age-related diseases.