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

Jing Hou, Kai-Xuan Chen, Qiao-Ni Xiao, Chen Hu, Jie Wei, Yang-Zi Jiang, Chao Zeng, Guang-Hua Lei, Yi-Lun Wang, Chang-Jun Li

1. 01

   D+Q effects on aging hallmarks are tissue- and cell-type-specific rather than uniform

2. 02

   D+Q enhanced immune cell function while maintaining population stability, reduced tissue inflammation and improved metabolic profiles

3. 03

   Intervention started during EARLY aging and continued long term mitigated aging readouts more than short, late-stage courses

4. 04

   Senescent-cell clearance by D+Q was incomplete, consistent with known off-target and haematologic effects

Study Design

preclinical

Sample Size

Not reported

Study Duration

Comparison of short late-stage vs prolonged early-initiated dosing in aged mice

Methodology

Unbiased multitissue single-cell and integrative transcriptomic analysis in naturally aged mice across aging phenotypes and tissue contexts, with histopathology and molecular profiling; comparison of early vs late initiation and short vs prolonged dosing.

Limitations

Preclinical mouse study only; no human data and no lifespan endpoint. The timing comparison is described by the authors as a tendency rather than a formally powered head-to-head schedule trial. Findings do not license earlier initiation or longer courses of D+Q in humans, where the only completed brain-endpoint trial was biomarker-null and haematologic toxicity is a known constraint on chronic dosing.