circHERC1-A telomerase activator.

Yumeng Cui, Yingying He, Xiaojie Wu, Yunzhu Dong, Yanghua Li, Weiling Man, Xiang Li, Shiyun Chen, Fang Pang, Ying Li, Hongbo Cheng, Congwen Wei, Zengchun Ma, Shuiping Chen, Yanli Lin, Junjie Xu, Youliang Wang

Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, China. · pubmed

Paper

Abstract

Telomerase, crucial for maintaining telomere integrity and genomic stability, is typically silenced in somatic cells with advancing age. In this study, we identify circHERC1 as a regulator of telomerase reverse transcriptase (TERT) transcription. Specifically, circHERC1 binds to the TERT promoter, facilitating the recruitment of RNA polymerase II and c-Fos, thereby activating TERT expression. Notably, circHERC1 expression exhibits a decline with age, which correlates with reduced telomerase activity. Restoration of circHERC1 expression enhances telomerase activity, promotes telomere elongation, and reverses aging-associated phenotypes. Furthermore, delivery of circHERC1 using adeno-associated virus vectors or extracellular vesicles effectively restores telomerase activity, preserves telomere integrity, and mitigates senescence. This intervention leads to improvements in cognitive function, physical performance, and a reduction in inflammation. These findings highlight the important role of circHERC1 in telomerase regulation and the aging process, positioning it as a potential therapeutic target for antiaging interventions.

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Research summary

The paper claims that circHERC1 activates telomerase expression, which enhances telomere elongation and reverses aging-associated phenotypes. This research addresses a potential mechanism for combating aging by targeting telomerase activity, which is directly related to longevity and age-related decline.

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