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Title: Mechanical Stress Triggers Premature Senescence in Cardiac Fibroblasts
Abstract The cardiovascular system functions under continuous cyclic mechanical stretch, with disruptions in mechanical and biochemical signals contributing to disease progression. In cardiovascular disorders, these disruptions activate cardiac fibroblasts (CFs) and promote cellular senescence, yet it remains unclear whether mechanical stimuli alone can initiate this phenotype. Here, primary murine CFs are exposed to uniaxial stretch, and systematically varied mechanical parameters assessed their role in senescence induction. Loss of stretch magnitude and increase in frequency, mimicking a pathologic hypertrophy and fibrosis, led to a senescence phenotype, identified through cell cycle arrest, decreased lamin B expression, and DNA damage. Mechanically‐induced CF senescence depends on p53/p21, whereas senescence triggered by oxidative stress or lamin A/C mutation proceeded via p16. Notably, mechanically‐induced premature senescence is accompanied by reduced levels of the nuclear envelope protein emerin. These findings demonstrate that altered mechanical signals are sufficient to trigger premature senescence and implicate compromised nuclear integrity in the underlying mechanism.  more » « less
Award ID(s):
2212121
PAR ID:
10640275
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Advanced Science
ISSN:
2198-3844
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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