Abstract
Senescent cells (SnCs) are increasingly recognized as key contributors to osteoarthritis, with conventional strategies centered on their elimination. However, senolytic approaches face mounting limitations, driving the need for refined interventions. Here, we exploit SnCs’ lipid metabolic signature to develop a senotherapeutic strategy. Given the universal lipid accumulation in SnCs and the dual role of lipids as both metabolic liabilities and essential lubricants, we engineer an injectable nanoliposuction hydrogel platform designed for “waste recycling”. This system removes excess lipids to mitigate senescence-associated secretory phenotype (SASP) propagation and incorporates the harvested lipids as a pivotal component of the biomimetic lubricating system, thereby alleviating mechanical allodynia and cartilage wear. This strategy circumvents potential side effects associated with direct SnCs clearance and repurposes these traditionally harmful cells as functional resources. Our findings establish a shift in the philosophy of senescence therapy, transitioning the focus from destructive ablation to spatially adaptive reallocation of metabolites.
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Data availability
The main data supporting the findings of this study are presented in the paper and its supplementary information. The raw mass spectrometry proteomics data generated in this study have been deposited in the iProX database (https://www.iprox.cn/), under accession number IPX0012242000. Source data are provided with this paper.
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Acknowledgements
This work was supported by grants from the National Nature Science Fund of China (82201729 to Z.Q., 82501891 to J.H., 8251101103 to Safwat Adel Abdo Moqbel, 82072413 and 82101649 to Y.Q.), the Natural Science Foundation of Zhejiang Province (LMS25H060001 to Y.Q.), the Key R&D Program of Zhejiang Province (2021C03108 to G.F.), and the Joint Construction Project of Zhejiang Province and Health Ministry (WKJ-ZJ-2029 to G.F.). We thank Safwat Adel Abdo Moqbel for providing financial support during the revision of this article. We thank Professor Ruikang Tang from Zhejiang University for his invaluable help in clarifying and structuring the research ideas for this paper. We thank Ms. Xiaoye Li and the Center for Basic and Translational Research at the Second Affiliated Hospital of Zhejiang University School of Medicine for their laboratory management and technical support. We thank Xiaoxing Wu from the Small Animal Experiment Center of the Second Affiliated Hospital of Zhejiang University School of Medicine for her valuable assistance with our animal studies. We thank Turtle Tech Ltd. (Shanghai, China) for their technical guidance on PCR and for their assistance with primer design and validation. We thank Shanghai Applied Protein Technology Co., Ltd. for their help with proteomics, Jingyao Chen from the core facility plat form of Zhejiang University School of Medicine for their technical support and Shanghai Bioprofile Technology Co., Ltd. for their help with scRNA-seq analysis. We thank Wendi Chen and Jiawen Sun (from Scientific Compass www.shiyanjia.com) for providing invaluable assistance with the material mechanical property testing and the friction experiment related testing, respectively.
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X.J., X.H., P.T., Y.W., J.Z., K.X., C.L., X.W. and K.W. performed the experimental operations. X.J. and H.C. performed the analysis and visualization of the single-cell data. X.J., Z.Q., J.W. and Z.L. completed the design and preparation of MINH. X.J. and H.Z. completed the related experiments and analysis of p16-3MR mice. Y.Q., Z.Q., G.J., S.Y., W.L. and G.F. supervised this project. X.J. conceived and designed the study. X.J. and Y.Q. completed the conceptual integration and manuscript writing.
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Ji, X., He, X., Cai, H. et al. Recycling senescent cell lipids for targeted senotherapy. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70486-0
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DOI: https://doi.org/10.1038/s41467-026-70486-0
