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Computational identification of natural senotherapeutic compounds that mimic dasatinib based on gene expression data
Franziska Meiners1, Burkhard Hinz2, Lars Boeckmann3
1Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany.
Abstract:
The major risk factor for chronic disease is chronological age, and age-related chronic diseases account for the majority of deaths worldwide. Targeting senescent cells that accumulate in disease-related tissues presents a strategy to reduce disease burden and to increase healthspan. The senolytic combination of the tyrosine-kinase inhibitor dasatinib and the flavonol quercetin is frequently used in clinical trials aiming to eliminate senescent cells. Here, our goal was to computationally identify natural senotherapeutic repurposing candidates that may substitute dasatinib based on their similarity in gene expression effects. The natural senolytic piperlongumine (a compound found in long pepper), and the natural senomorphics parthenolide, phloretin and curcumin (found in various edible plants) were identified as potential substitutes of dasatinib. The gene expression changes underlying the repositioning highlight apoptosis-related genes and pathways. The four compounds, and in particular the top-runner piperlongumine, may be combined with quercetin to obtain natural formulas emulating the dasatinib + quercetin formula.
Insights
Researchers identified natural compounds like piperlongumine as potential replacements for dasatinib in senolytic therapies. These senotherapeutics may be combined with quercetin to target aging and chronic diseases by eliminating senescent cells.
Area of Science:
- Gerontology
- Pharmacology
- Computational Biology
Background:
- Aging is the primary risk factor for chronic diseases, leading to significant global mortality.
- Senescent cells accumulate in tissues with age and disease, presenting a therapeutic target to improve healthspan.
- The combination of dasatinib and quercetin is a common senolytic treatment in clinical trials.
Purpose of the Study:
- To computationally identify natural compounds that can replace dasatinib in senolytic therapy.
- To find natural senotherapeutic candidates with similar gene expression effects to dasatinib.
Main Methods:
- Gene expression analysis to compare natural compounds with dasatinib.
- Computational identification of senotherapeutic repurposing candidates.
- Evaluation of natural senolytics and senomorphics.
Main Results:
- Piperlongumine, parthenolide, phloretin, and curcumin were identified as potential natural substitutes for dasatinib.
- Gene expression changes indicate a role for apoptosis-related genes and pathways.
- Piperlongumine emerged as a top candidate for senolytic therapy.
Conclusions:
- Natural compounds, particularly piperlongumine, can potentially substitute dasatinib in senolytic treatments.
- These natural compounds, combined with quercetin, could form new senolytic formulas.
- Targeting senescent cells with natural senotherapeutics offers a strategy to combat age-related diseases.
