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Profiling the molecular and physiological effects of senolytic treatment on aged mice identifies immune, fibrotic and metabolic remodeling.

Created on 18 Jun 2026

Authors

Jing Hou, Kai-Xuan Chen, Qiao-Ni Xiao, Chen Hu, Jie Wei, Yang-Zi Jiang, Ling Liu, Chen He, Mei Huang, Yu-Rui Jiao, Xiang Tang, Nan-Yu Zou, Wen-Zhen He, Yu-Chen Sun, Yue-Ying Zhou, Xi Huang, Chao Zeng, Guang-Hua Lei, Yi-Lun Wang, Chang-Jun Li

Published in

Nature aging. Jun 17, 2026. Epub Jun 17, 2026.

Abstract

Although senolytics such as dasatinib and quercetin (D+Q) show promise in modulating aging, their tissue-specific efficacy and optimal intervention timing remain poorly understood. Given D+Q's potential off-target effects, incomplete senescent cell clearance and associated hematologic side effects, we performed an unbiased multitissue single-cell analysis in aged mice across different aging phenotypes and tissue contexts. Here through integrative transcriptomics, single-cell technologies, histopathology and molecular profiling, we investigated the influence of D+Q treatment on aging-related phenotypes at the tissue and cellular levels. Specifically, D+Q remodeled immunity by enhancing immune cell function and maintaining population stability, alleviated tissue inflammation and improved metabolic profiles. Furthermore, intervention initiated during early aging and prolonged treatment showed a greater tendency to mitigate readouts of aging compared to shorter, late-stage treatment. Our findings reveal that D+Q systematically attenuates several aging hallmarks in a tissue- and cell-type-specific manner, and support the possibility that early-initiated, long-term intervention may amplify efficacy.

PMID:
42310394
Bibliographic data and abstract were imported from PubMed on 18 Jun 2026.

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