首页|EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1,TRF2,and RAD50

EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1,TRF2,and RAD50

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Telomeres are nucleoprotein structures located at the end of each chromosome, which function in terminal protection and genomic stability. Telomeric damage is closely related to replicative senescence in vitro and physical aging in vivo. As relatively long-lived mammals based on body size,bats display unique telomeric patterns, including the up-regulation of genes involved in alternative lengthening of telomeres (ALT), DNA repair, and DNA replication. At present, however, the relevant molecular mechanisms remain unclear. In this study, we performed cross-species comparison and identified EPAS1, a well-defined oxygen response gene, as a key telomeric protector in bat fibroblasts. Bat fibroblasts showed high expression of EPAS1, which enhanced the transcription of shelterin components TRF1 and TRF2, as well as DNA repair factor RAD50, conferring bat fibroblasts with resistance to senescence during long-term consecutive expansion.Based on a human single-cell transcriptome atlas, we found that EPAS1 was predominantly expressed in the human pulmonary endothelial cell subpopulation. Using in vitro-cultured human pulmonary endothelial cells, we confirmed the functional and mechanistic conservation of EPAS1 in telomeric protection between bats and humans.In addition, the EPAS1 agonist M1001 was shown to be a protective compound against bleomycin-induced pulmonary telomeric damage and senescence. In conclusion, we identified a potential mechanism for regulating telomere stability in human pulmonary diseases associated with aging, drawing insights from the longevity of bats.

BatTelomereSenescenceEPAS1M1001Pulmonary endothelial cell

Kai-Qin Li、Gao-Jing Liu、Xiu-Yun Liu、Qiong-Fang Chen、Xiao-Yan Huang、Qiu Tu、Jiao Zhang、Qing Chang、Yun-Hua Xie、Rong Hua、Dong-Ming Xu、Zhen Liu、Bo Zhao

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Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province,KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China

University of Chinese Academy of Sciences,Beijing 100049,China

Primate Facility,National Research Facility for Phenotypic & Genetic Analysis of Model Animals,and National Resource Center for Non-Human Primates,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,Chi

State Key Laboratory of Genetic Resources and Evolution,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan 650201,China

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Applied Basic Research Programs of Science and Technology Commission Foundation of Yunnan ProvinceNational Key Research & Developmental Program of ChinaChinese Academy of Sciences(CAS) "Light of West China" ProgramKunming Science and Technology Bureau

202201AS0700442021YFA0805701xbzgzdsys-2021132022SCP007

2023

10.24272/j.issn.2095-8137.2022.531

动物学研究
中国科学院昆明动物研究所 中国动物学会

动物学研究

CSTPCDCSCD
影响因子：0.582
ISSN：0254-5853
年,卷(期)：2023.44(3)
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