Open AccessRestoration of senescent human diploid fibroblasts by modulation of the extracellular matrix
Author(s) -
Choi Hae Ri,
Cho Kyung A,
Kang Hyun Tae,
Lee Jung Bin,
Kaeberlein Matt,
Suh Yousin,
Chung In Kwon,
Park Sang Chul
Publication year - 2011
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2010.00654.x
Subject(s) - biology , extracellular matrix , ploidy , microbiology and biotechnology , matrix (chemical analysis) , fibroblast , genetics , gene , cell culture , materials science , composite material
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.