Science advances · 2022

ETS1 acts as a regulator of human healthy aging via decreasing ribosomal activity

Xiao, F. and Yu, Q. and Deng, Z. and Yang, K. and Ye, Y. and Ge, M. and Yan, D. and Wang, H. and Chen, X. and Yang, L. and Yang, B. and Lin, R. and Zhang, W. and Yang, X. and Dong, L. and He, Y. and Zhou, J. and Cai, W. and Li, J. and Kong, Q.

doi:10.1126/sciadv.abf2017

Abstract

Adaptation to reduced energy production during aging is a fundamental issue for maintaining healthspan or prolonging life span. Currently, however, the underlying mechanism in long-lived people remains poorly understood. Here, we analyzed transcriptomes of 185 long-lived individuals (LLIs) and 86 spouses of their children from two independent Chinese longevity cohorts and found that the ribosome pathway was significantly down-regulated in LLIs. We found that the down-regulation is likely controlled by ETS1 (ETS proto-oncogene 1), a transcription factor down-regulated in LLIs and positively coexpressed with most ribosomal protein genes (RPGs). Functional assays showed that ETS1 can bind to RPG promoters, while ETS1 knockdown reduces RPG expression and alleviates cellular senescence in human dermal fibroblast (HDF) and embryonic lung fibroblast (IMR-90) cells. As protein synthesis/turnover in ribosomes is an energy-intensive cellular process, the decline in ribosomal biogenesis governed by ETS1 in certain female LLIs may serve as an alternative mechanism to achieve energy-saving and healthy aging.

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Science advances 2022

ETS1 acts as a regulator of human healthy aging via decreasing ribosomal activity

Xiao, F. and Yu, Q. and Deng, Z. and Yang, K. and Ye, Y. and Ge, M. and Yan, D. and Wang, H. and Chen, X. and Yang, L. and Yang, B. and Lin, R. and Zhang, W. and Yang, X. and Dong, L. and He, Y. and Zhou, J. and Cai, W. and Li, J. and Kong, Q.

doi:10.1126/sciadv.abf2017

Abstract

Adaptation to reduced energy production during aging is a fundamental issue for maintaining healthspan or prolonging life span. Currently, however, the underlying mechanism in long-lived people remains poorly understood. Here, we analyzed transcriptomes of 185 long-lived individuals (LLIs) and 86 spouses of their children from two independent Chinese longevity cohorts and found that the ribosome pathway was significantly down-regulated in LLIs. We found that the down-regulation is likely controlled by ETS1 (ETS proto-oncogene 1), a transcription factor down-regulated in LLIs and positively coexpressed with most ribosomal protein genes (RPGs). Functional assays showed that ETS1 can bind to RPG promoters, while ETS1 knockdown reduces RPG expression and alleviates cellular senescence in human dermal fibroblast (HDF) and embryonic lung fibroblast (IMR-90) cells. As protein synthesis/turnover in ribosomes is an energy-intensive cellular process, the decline in ribosomal biogenesis governed by ETS1 in certain female LLIs may serve as an alternative mechanism to achieve energy-saving and healthy aging.

Back to publications

Central South University Xiangya Hospital Li Lab Skin Aging and Hair Regeneration Research Center