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An Unbiased Cell‐Culture Selection Yields DNA Aptamers as Novel Senescent Cell‐Specific Reagents
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An Unbiased Cell‐Culture Selection Yields DNA Aptamers as Novel Senescent Cell‐Specific Reagents
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Journal Article
An Unbiased Cell‐Culture Selection Yields DNA Aptamers as Novel Senescent Cell‐Specific Reagents
2025
Overview
ABSTRACT
Cellular senescence is an irreversible form of cell‐cycle arrest caused by excessive stress or damage. While various biomarkers of cellular senescence have been proposed, there are currently no universal, stand‐alone indicators of this condition. The field largely relies on the combined detection of multiple biomarkers to differentiate senescent cells from non‐senescent cells. Here we introduce a new approach: unbiased cell culture selections to identify senescent cell‐specific folded DNA aptamers from vast libraries of trillions of random 80‐mer DNAs. Senescent mouse adult fibroblasts and their non‐senescent counterparts were employed for selection. We demonstrate aptamer specificity for senescent mouse cells in culture, identify a form of fibronectin as the molecular target of two selected aptamers, show increased aptamer staining in naturally aged mouse tissues, and demonstrate decreased aptamer staining when p16 expressing cells are removed in a transgenic INK‐ATTAC mouse model. This work demonstrates the value of unbiased cell‐based selections to identify new senescence‐specific DNA reagents.
Pearson et al. report the selection of DNA aptamers against senescent mouse cells, demonstrating broad binding specificity for multiple senescent mouse cell types and induction methods. Two of the aptamers bind a form of fibronectin with sub‐nanomolar affinity even in complex protein mixtures. One aptamer detects age‐ and senescence‐associated changes in mouse lung tissue, highlighting the ability of DNA aptamer selection against a senescence phenotype to generate powerful new reagents with the potential to detect or target senescent cells.
Publisher
John Wiley & Sons, Inc
Subject
/ aptamer
/ Aptamers
/ Aptamers, Nucleotide - chemistry
/ Aptamers, Nucleotide - metabolism
/ Cell Culture Techniques - methods
/ Cellular Senescence - genetics
/ Cyclin-Dependent Kinase Inhibitor p16 - genetics
/ Cyclin-Dependent Kinase Inhibitor p16 - metabolism
/ DNA
/ Humans
/ Kinases
/ Mice
/ SELEX
