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Exploring the fuzzy border between senolytics and senomorphics with chemoinformatics and systems pharmacology
Kevin Samael Olascoaga-Del Angel1,2, Humberto Gutierrez3, Mina Königsberg2
1Posgrado en Biología Experimental, DCBS, Universidad Autónoma Metropolitana Iztapalapa, Mexico City, Mexico.
Biogerontology
|July 5, 2022
Summary
Senolytics and senomorphics, used to combat aging and disease, share similar properties. Understanding these similarities is key to developing more effective senotherapies.
Area of Science:
- Gerontology and Pharmacology
- Cellular Biology and Aging
- Biochemistry and Drug Discovery
Background:
- Senescent cells accumulate with age, releasing pro-inflammatory factors (SASP) that drive chronic diseases.
- Senolytics eliminate senescent cells, while senomorphics reduce SASP-related inflammation.
- Clear definitions of senolytic and senomorphic properties are lacking, hindering senotherapy development.
Purpose of the Study:
- To compare physicochemical, structural, and pharmacological properties of senolytics and senomorphics.
- To identify key characteristics for effective and selective senotherapeutic agents.
- To provide a basis for designing novel senotherapies.
Main Methods:
- Chemoinformatic and systems pharmacology analysis.
- Comparative analysis of 84 senolytics and 79 senomorphics.
- Transcriptome perturbation analysis to assess cellular responses.
Main Results:
- Significant physicochemical, structural, and pharmacological similarities were found between senolytics and senomorphics.
- These similarities were also evident in their effects on cellular transcriptome.
- Overlap in properties may explain dual activity observed in some molecules.
Conclusions:
- Senolytics and senomorphics exhibit overlapping properties, suggesting a shared underlying mechanism.
- This understanding can guide the design of more effective and selective senotherapeutic drugs.
- Future research should leverage these insights for improved senotherapy development.
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