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Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice
Cell Res. 2020 Jul;30(7):574-589. doi: 10.1038/s41422-020-0314-9.
Yusheng Cai # 1, Huanhuan Zhou # 1 2, Yinhua Zhu # 3 4, Qi Sun 1, Yin Ji 1, Anqi Xue 1, Yuting Wang 1, Wenhan Chen 1, Xiaojie Yu 1, Longteng Wang 5, Han Chen 4, Cheng Li 6, Tuoping Luo 7 8, Hongkui Deng 9 10
Abstract:
...Herein, we developed a prodrug strategy to design a new compound based on the increased activity of lysosomal β-galactosidase (β-gal), a primary characteristic of senescent cells. Our prodrug SSK1 is specifically activated by β-gal and eliminates mouse and human senescent cells independently of senescence inducers and cell types. In aged mice, our compound effectively cleared senescent cells in different tissues, decreased the senescence- and age-associated gene signatures, attenuated low-grade local and systemic inflammation, and restored physical function. Our results demonstrate that lysosomal β-gal can be effectively leveraged to selectively eliminate senescent cells, providing a novel strategy to develop anti-aging interventions.
PMID: 32341413
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184167/