Decoding aging-dependent regenerative decline across tissues at single-cell resolution

Cai, Yusheng; Xiong, Muzhao; Xin, Zijuan; Liu, Chengyu; Ren, Jie; Yang, Xiying; Lei, Jinghui; Li, Wei; Liu, Feifei; Chu, Qun; Zhang, Yiyuan; Yin, Jian; Ye, Yanxia; Liu, Dingyi; Fan, Yanling; Sun, Shuhui; Jing, Yaobin; Zhao, Qian; Zhao, Liyun; Che, Shanshan; Zheng, Yandong; Yan, Haoteng; Ma, Shuai; Wang, Si; Izpisua Belmonte, Juan Carlos; Qu, Jing; Zhang, Weiqi; Liu, Guang-Hui

doi:10.1016/j.stem.2023.09.014

Cited by 6 publications

(2 citation statements)

References 103 publications

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“…1 , Table 1 ). This finding was confirmed in a recent scRNA-seq atlas of murine cell types across tissues, ages, and conditions [ 128 ], and by numerous independent histology-based efforts. Increased expression of inflammation and immunoregulatory marker genes furthermore characterizes the aging endothelium across many tissues (Fig.…”

Section: Discussion and Future Directionssupporting

confidence: 60%

A high-resolution view of the heterogeneous aging endothelium

Dobner,

Tóth,

de Rooij

2024

Angiogenesis

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Vascular endothelial cell (EC) aging has a strong impact on tissue perfusion and overall cardiovascular health. While studies confined to the investigation of aging-associated vascular readouts in one or a few tissues have already drastically expanded our understanding of EC aging, single-cell omics and other high-resolution profiling technologies have started to illuminate the intricate molecular changes underlying endothelial aging across diverse tissues and vascular beds at scale. In this review, we provide an overview of recent insights into the heterogeneous adaptations of the aging vascular endothelium. We address critical questions regarding tissue-specific and universal responses of the endothelium to the aging process, EC turnover dynamics throughout lifespan, and the differential susceptibility of ECs to acquiring aging-associated traits. In doing so, we underscore the transformative potential of single-cell approaches in advancing our comprehension of endothelial aging, essential to foster the development of future innovative therapeutic strategies for aging-associated vascular conditions.

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Section: Discussion and Future Directionssupporting

confidence: 60%

A high-resolution view of the heterogeneous aging endothelium

Dobner,

Tóth,

de Rooij

2024

Angiogenesis

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“…Moreover, the SASP derived from senescent ECs transmits injury signals to other vascular cells and nonvascular tissues/organs, ultimately resulting in extensive cellular senescence. The emergence of abnormal tissue inflammation, increased cell death, and decreased neovascularization capacity are crucial factors contributing to regenerative dysfunction in senescent tissues. , Currently, therapeutic strategies available for senescent ECs have been proven effective in ameliorating aging-induced organ dysfunction . Furthermore, recent studies have suggested that insufficient vascular endothelial growth factor (VEGF) signaling may drive physiological aging in multiple organ systems.…”

Section: Introductionmentioning

confidence: 99%

A Nanocapsule System Combats Aging by Inhibiting Age-Related Angiogenesis Deficiency and Glucolipid Metabolism Disorders

Li,

Zhang,

Cheng

et al. 2024

ACS Nano

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Insufficient angiogenic stimulation and dysregulated glycolipid metabolism in senescent vascular endothelial cells (VECs) constitute crucial features of vascular aging. Concomitantly, the generation of excess senescenceassociated secretory phenotype (SASP) and active immune-inflammatory responses propagates within injured vessels, tissues, and organs. Until now, targeted therapies that efficiently rectify phenotypic abnormalities in senescent VECs have still been lacking. Here, we constructed a Pd/hCeO 2 −BMS309403@platelet membrane (PCBP) nanoheterostructured capsule system loaded with fatty acid-binding protein 4 (FABP4) inhibitors and modified with platelet membranes and investigated its therapeutic role in aged mice. PCBP showed significant maintenance in aged organs and demonstrated excellent biocompatibility. Through cyclic tail vein administration, PCBP extended the lifespan and steadily ameliorated abnormal phenotypes in aged mice, including SASP production, immune and inflammatory status, and age-related metabolic disorders. In senescent ECs, PCBP mediated the activation of vascular endothelial growth factor (VEGF) signaling and glycolysis and inhibition of FABP4 by inducing the synthesis of hypoxia-inducible factor-1α, thereby reawakening neovascularization and restoring glycolipid metabolic homeostasis. In conclusion, the PCBP nanocapsule system provides a promising avenue for interventions against aging-induced dysfunction.

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