Abstract
Precise detection of cellular senescence may allow its role in biological systems to be evaluated more effectively, while supporting studies of therapeutic candidates designed to evade its detrimental effect on physical function. We report here studies of α-l-fucosidase (α-fuc) as a biomarker for cellular senescence and the development of an α-fuc-responsive aggregation induced emission (AIE) probe, termed QM-NHαfuc designed to complement more conventional probes based on β-galactosidase (β-gal). Using QM-NHαfuc, the onset of replicative-, reactive oxygen species (ROS)-, ultraviolet A (UVA)-, and drug-induced senescence could be probed effectively. QM-NHαfuc also proved capable of identifying senescent cells lacking β-gal expression. The non-invasive real-time senescence tracking provided by QM-NHαfuc was validated in an in vivo senescence model. The results presented in this study lead us to suggest that the QM-NHαfuc could emerge as a useful tool for investigating senescence processes in biological systems.
Highlights
With such considerations in mind, we developed the a-fuc responsive uorogenic probe (QM-NHafuc) that serves to light up senescent cells through an aggregation induced emission (AIE) process in vitro and in vivo (Fig. 1B)
In an effort to determine whether a-fuc represents a good target for senescence probe development, we tested its expression in different senescence models including replicative and stressinduced premature senescent cells
Inspired by the everincreasing utility of the so-called AIE strategy in developing enzyme activatable probes,[38,39,40] we developed an a-fuc responsive AIE luminogen (AIEgen), QM-NHafuc, designed to permit the real-time detection of senescent cells
Summary
Senescence is a stable state of irreversible cell-cycle arrest necessary for preventing the proliferation of damaged cells,[1,2,3] promoting tissue remodeling,[4,5] and maintaining organism homeostasis.[6,7] The improper elimination of senescent cells can negatively affect the regenerative capabilities of tissues, contributing to local in ammation, age-related degenerative diseases, and cancer stemness and metastasis.[8,9,10,11,12] In recent decades, studies of cellular senescence have translated into innovative discoveries. Edge Article localized in lysosome) and plasma a-fuc encoded by FUCA1 and FUCA2, respectively.[32] Recent research provides support for the suggestion that mRNA expression levels and the enzymatic activity of a-fuc encoded by FUCA1 are upregulated across multiple canonical senescence types, including oncogene-, drug-induced, and replicative cellular senescence.[33] In the context of the present study, we have con rmed that a-fuc activity is upregulated in diverse senescence models and is correlated with the molecular pathways leading to senescence. With such considerations in mind, we developed the a-fuc responsive uorogenic probe (QM-NHafuc) that serves to light up senescent cells through an AIE process in vitro and in vivo (Fig. 1B).
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