New methods for dynamic monitoring of cellular senescence based on metabolite biosensors

作者：Ao-Xue WANG, Jiao-Ni CHI, Ya-Le XIA, Ya-Qiong CHEN, Zhuo ZHANG, Yu-Zheng ZHAO · 发表于：Shengming kexue · 年份：2026 · DOI：10.3724/cbls.2026099 · 研究领域：Telomeres, Telomerase, and Senescence、Mechanisms of cancer metastasis、Advanced Fluorescence Microscopy Techniques

Cellular senescence can be induced through multiple mechanisms, including telomere shortening, DNA damage, replicative stress via oncogene activation, oxidative stress, mitochondrial dysfunction, and metabolic remodeling. A prominent challenge in current research is that biomarkers commonly used to identify cellular senescence, such as cellular morphology remodeling, β-galactosidase activity, expression of key genes like p16, senescence-associated secretory phenotypes, and DNA damage foci, are difficult to use for tracking the dynamic changes of senescence in living cells or capturing phenotypic heterogeneity among cells. Here, we propose a novel metabolite-biosensor-based approach to dynamically detect cellular senescence. Metabolic remodeling is not only a hallmark of cellular senescence but also a crucial driver of its progression. By using genetically encoded fluorescent sensors, this method will not only enable real-time, in situ visualization of senescent cell phenotypes at the single-cell and subcellular level, but also offer new insights into the metabolic roots of cellular senescence, making it a powerful tool for studying metabolic senescence. Considering the universality and specificity of metabolites as senescence biomarkers, we highlight a few key metabolites closely associated with cellular senescence, including NAD + , lactose/galactose, α-ketoglutarate, and polyamines, and summarize their fluctuations and roles in organismal and cellular aging, as well as the ...