ERG phase separation attenuates cellular senescence.

Lu Pu, Zhiliang Zuo, Hui Zheng, Rui Ou, Ru Gao, Zhaomin Deng, Xiaochu Wu, Chun Xiao, Meiling Ge, Lixing Zhou, Haoran Jin, Shaochong Qi, Fengjuan Hu, Jieli Chen, Hang Li, Yan Zhao, Birong Dong, Hao Jiang

Laboratory for Aging and Cancer Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.Laboratory for Aging and Cancer Research, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. · pubmed

Paper

Abstract

Centenarians, individuals who reach extreme old age, provide a valuable model for understanding mechanisms associated with healthy aging. Using ATAC-seq and transcriptomic profiling of peripheral blood mononuclear cells from centenarians, we identified a distinct chromatin accessibility landscape linked to exceptional longevity. Integrative analysis highlighted the E-26 transformation-specific (ETS)-related transcription factor ERG as a longevity-associated regulator. Functional studies in human cells showed that ERG forms nuclear condensates through liquid-liquid phase separation, a property associated with altered chromatin organization and reduced expression of senescence-related genes, including CDKN2A. Consistent with these effects, ERG condensation was associated with attenuation of cellular senescence phenotypes. Together, these findings connect epigenomic features observed in centenarians with transcription factor biophysical properties and cellular aging control, highlighting phase separation as a regulatory layer that may contribute to cellular resilience during aging.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

ERG phase separation reduces cellular senescence by altering chromatin organization and gene expression. The study connects epigenomic features in centenarians to mechanisms of aging, addressing root causes of cellular aging rather than merely treating symptoms.

Author of this paper? Send a correction.