Generative Molecular Design for Senescence-Associated Secretory Phenotype (SASP) Reversal: A REINVENT4 Pipeline Trained on Real LINCS L1000 Transcriptomic Data
Uysal SA
Research Square · 29 Sep 2026 · Preprint, not yet peer-reviewed
The senolytic combination improved liver fibrosis without disease worsening in nearly half of treated participants while lowering cellular senescence markers.
Researchers identified a p53-p21-Cyclin D2 axis that governs senescent macrophages in mice and human liver cirrhosis and can be cleared with senolytics.
The new blood-based tools estimate senescence gene activity to predict incident diseases, all-cause mortality, and clinical treatment responses.
Monitored by serum transaminase levels, low doses of the drug alleviated age-related pathologies without causing the hepatotoxicity seen at higher doses.
The proteomic biomarker tracked chronic illness risk in the UK Biobank and shifted following an 18-month multimodal exercise intervention.
