Senolytic and senomorphic agent procyanidin C1 alleviates structural and functional decline in the aged retina

• 成果类型: Article
• 署名作者: Liu, Yidan; Liu, Xiuxing; Chen, Xuhao; Yang, Zhenlan; Chen, Jianqi; Zhu, Weining; Li, Yangyang; Wen, Yuwen; Deng, Caibin; Gu, Chenyang; Lv, Jianjie; Ju, Rong; Zhuo, Yehong; Su, Wenru
• 署名单位: Sun Yat Sen University; Sun Yat Sen University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15393
• DOI: 10.1073/pnas.2311028121
• 发表日期: 2024-04-30
• 关键词: cellular senescence; inflammation; microglia; ganglion; disease

摘要

Increased cellular senescence burden contributes in part to age- related organ dysfunction and pathologies. In our study, using mouse models of natural aging, we observed structural and functional decline in the aged retina, which was accompanied by the accumulation of senescent cells and senescence- associated secretory phenotype factors. We further validated the senolytic and senomorphic properties of procyanidin C1 (PCC1) both in vitro and in vivo, the long- term treatment of which ameliorated age- related retinal impairment. Through high- throughput single- cell RNA sequencing (scRNA- seq), we comprehensively characterized the retinal landscape after PCC1 administration and deciphered the molecular basis underlying the senescence burden increment and elimination. By exploring the scRNA- seq database of age- related retinal disorders, we revealed the role of cellular senescence and the therapeutic potential of PCC1 in these pathologies. Overall, these results indicate the therapeutic effects of PCC1 on the aged retina and its potential use for treating age- related retinal disorders.