Research Papers:

Apoptotic transition of senescent cells accompanied with mitochondrial hyper-function

Danli Wang _, Yang Liu, Rui Zhang, Fen Zhang, Weihao Sui, Li Chen, Ran Zheng, Xiaowen Chen, Feiqiu Wen, Hong-Wei Ouyang and Junfeng Ji

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Oncotarget. 2016; 7:28286-28300. https://doi.org/10.18632/oncotarget.8536

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Danli Wang1, Yang Liu1, Rui Zhang1, Fen Zhang1, Weihao Sui1, Li Chen1, Ran Zheng1, Xiaowen Chen3, Feiqiu Wen3, Hong-Wei Ouyang1,2, Junfeng Ji1,2

1Center of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China

2Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, China

3Division of Hematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, China

Correspondence to:

Junfeng Ji, e-mail: [email protected]

Hong Wei Ouyang, e-mail: [email protected]

Feiqiu Wen, e-mail: [email protected]

Keywords: senescence, metabolism, mitochondria, ROS, apoptosis

Received: June 29, 2015    Accepted: March 06, 2016    Published: April 1, 2016


Defined as stable cell-cycle arrest, cellular senescence plays an important role in diverse biological processes including tumorigenesis, organismal aging, and embryonic development. Although increasing evidence has documented the metabolic changes in senescent cells, mitochondrial function and its potential contribution to the fate of senescent cells remain largely unknown. Here, using two in vitro models of cellular senescence induced by doxorubicin treatment and prolonged passaging of neonatal human foreskin fibroblasts, we report that senescent cells exhibited high ROS level and augmented glucose metabolic rate concomitant with both morphological and quantitative changes of mitochondria. Furthermore, mitochondrial membrane potential depolarized at late stage of senescent cells which eventually led to apoptosis. Our study reveals that mitochondrial hyper-function contributes to the implementation of cellular senescence and we propose a model in which the mitochondrion acts as the key player in promoting fate-determination in senescent cells.

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PII: 8536