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

Author:

Liu Yidan1ORCID,Liu Xiuxing1ORCID,Chen Xuhao1ORCID,Yang Zhenlan1ORCID,Chen Jianqi1ORCID,Zhu Weining2ORCID,Li Yangyang1,Wen Yuwen1ORCID,Deng Caibin1ORCID,Gu Chenyang1ORCID,Lv Jianjie1ORCID,Ju Rong1,Zhuo Yehong1,Su Wenru1ORCID

Affiliation:

1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, People’s Republic of China

2. Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510060, People’s Republic of China

Abstract

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.

Publisher

Proceedings of the National Academy of Sciences

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