Restoration of senescent human diploid fibroblasts by modulation of the extracellular matrix

Aging Cell

Hae Ri Choi⁴  Kyung A Cho¹  Hyun Tae Kang⁴  Jung Bin Lee²  Matt Kaeberlein⁵  Yousin Suh³  In Kwon Chung⁶ 

[1] Department of Biochemistry, Chonnam National University Medical School, Gwangju, South Korea;Department of Forensic Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, South Korea;Institute for Aging Research, Diabetes Research and Training Center;Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Institute on Aging, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, South Korea;Department of Pathology, University of Washington, Seattle, WA 98195, USA;Departments of Biology and Biomedical Sciences, Yonsei University, Seoul, South Korea

关键词: Aging;    cellular senescence;    extra cellular matrix;    Ku70;    SIRT1;   

DOI  :  10.1111/j.1474-9726.2010.00654.x

来源: Wiley

【 摘 要 】

Summary

Human diploid fibroblasts have the capacity to complete a finite number of cell divisions before entering a state of replicative senescence characterized by growth arrest, changes in morphology, and altered gene expression. Herein, we report that interaction with extracellular matrix (ECM) from young cells is sufficient to restore aged, senescent cells to an apparently youthful state. The identity of the restored cells as having been derived from senescent cells has been confirmed by a variety of methods, including time lapse live cell imaging and DNA finger print analysis. In addition to cell morphology, phenotypic restoration was assessed by resumption of proliferative potential, growth factor responsiveness, reduction of intracellular reactive oxygen species levels, recovery of mitochondrial membrane potential, and increased telomere length. Mechanistically, we find that both Ku and SIRT1 are induced during restoration and are required for senescent cells to return to a youthful phenotype. These observations demonstrate that human cellular senescence is profoundly influenced by cues from the ECM, and that senescent cell plasticity is much greater than that was previously believed to be the case.

【 授权许可】

Unknown   
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland