Fluorescence lifetime clocks quantify senescence and aging.

Chenxu Yan, Caiqi Liu, Bofang Liu, Qiaoqiao Zheng, Xingyuan Zhao, Sirui Lu, Xiaoqing Fu, Wennan Li, Juan Li, Dan Li, Yongkang Yao, Yutao Zhang, Huanhu Zhu, Ping Shi, Wei-Hong Zhu, Zhiqian Guo

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, China.Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, China. · pubmed

Paper

Abstract

Epigenetic and omics-based clocks have provided invaluable tools to quantify aging, yet these clocks do not provide direct readouts of aging in real-time in living systems. As methylation changes in nucleolar ribosomal DNA are reliably associated with aging and cellular senescence, we hypothesized that shifts in rRNA species could be leveraged to generate image-based clocks using selective dyes. Here we engineer sensitive and photostable hybrid polymethine dyes selective for rRNA. We present a fluorescence lifetime imaging strategy to visually quantify age- and cellular senescence-dependent nucleolar RNA changes that bypasses requirements for extensive sample preparation such as DNA isolation and enables in vivo, real-time age quantification. We demonstrate resolution through cellular to organismal scales and demonstrate translatability by generating clocks from cells and tissues, as well as Caenorhabditis elegans, mice and human samples. Our fluorescence lifetime imaging strategy thus enables in vivo measurements of aging and senescence and expands the toolbox for aging biology research and translation.

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Research summary

The paper claims that a fluorescence lifetime imaging strategy can quantify age- and senescence-dependent nucleolar RNA changes in real-time. This research is relevant as it addresses the quantification of aging and cellular senescence, which are fundamental aspects of longevity and aging biology.

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