Heterochronic parabiosis uncovers AdipoR1 as a critical player in retinal rejuvenation

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-07-16 DOI:10.1126/sciadv.adv6642

Yidan Liu, Xiuxing Liu, Jianjie Lv, Qi Zhang, Zhenlan Yang, Xuhao Chen, Chenyang Gu, Chun Zhang, Yehong Zhuo, Wenru Su

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Abstract

Aging induces substantial structural and functional decline in the retina, yet the molecular drivers of this process remain elusive. In this study, we used heterochronic parabiosis (HP) combined with single-cell RNA sequencing to generate comprehensive transcriptomic profiles of murine retinas from young, aged, and HP pairs, aiming to identify antiaging targets. Our analysis revealed extensive transcriptional alterations across retinal cell types with aging. HP experiments demonstrated that systemic factors from young mice rejuvenated aged retinas and alleviated senescent phenotypes, while aged blood accelerated aging in young mice. Integrative analysis pinpointed adiponectin receptor 1 (AdipoR1) and the downstream adenosine 5′-monophosphate–activated protein kinase (AMPK) signaling pathway as central to the molecular mechanisms underlying retinal rejuvenation. Treatment with the AdipoR1 agonist AdipoRon reversed retinal aging. Mechanistically, AdipoR1-AMPK activation promoted mitochondrial function, contributing to the restoration of youthful cellular phenotypes. Together, our study identifies AdipoR1 as a therapeutic target for retinal aging and provides insights into the molecular programs driving retinal rejuvenation.

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异慢性异种共生揭示了AdipoR1在视网膜年轻化中的关键作用

衰老会导致视网膜结构和功能的显著下降，但这一过程的分子驱动因素仍然难以捉摸。在这项研究中，我们利用异慢性异种共生（HP）结合单细胞RNA测序，从年轻、年老和HP对小鼠视网膜中获得全面的转录组图谱，旨在确定抗衰老靶点。我们的分析显示，随着年龄的增长，视网膜细胞类型发生了广泛的转录改变。HP实验表明，来自年轻小鼠的系统因子使衰老的视网膜恢复活力，减轻衰老表型，而衰老的血液加速了年轻小鼠的衰老。综合分析指出，脂联素受体1 （AdipoR1）和下游腺苷5 ' -单磷酸活化蛋白激酶（AMPK）信号通路是视网膜年轻化的分子机制的核心。用AdipoR1激动剂AdipoRon治疗可以逆转视网膜老化。在机制上，AdipoR1-AMPK激活促进线粒体功能，有助于恢复年轻细胞表型。总之，我们的研究确定了AdipoR1作为视网膜衰老的治疗靶点，并为驱动视网膜年轻化的分子程序提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.