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Deciphering the Causal Links Among Metabolomics, Ageing Phenotypes, and Pathological Scars: A Two-Sample Mendelian
1Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Clinical, Cosmetic and Investigational Dermatology
|May 18, 2026
Summary
This study reveals key blood metabolites and aging factors causally linked to hypertrophic scars and keloids. Findings identify Eugenol sulfate and Phenylacetylglutamate as potential targets for new metabolic scar treatments.
Area of Science:
- Genetics
- Metabolomics
- Dermatology
Background:
- Hypertrophic scars (HS) and keloids are complex skin conditions with poor treatment outcomes.
- The interaction between metabolism and aging may influence scar development.
- Identifying novel therapeutic targets is crucial for managing these conditions.
Purpose of the Study:
- To investigate causal links between blood metabolites, aging phenotypes (telomere length, epigenetic age), and HS/keloids.
- To explore the mediating roles of aging in metabolite-scar relationships.
- To identify potential therapeutic targets for scar prevention and treatment.
Main Methods:
- Utilized Two-sample Mendelian randomization (MR) and Two-step Mediation MR analysis.
- Integrated large-scale GWAS data for metabolites, telomere length, epigenetic age, HS, and keloids.
- Employed statistical methods to assess causality, heterogeneity, and pleiotropy.
Main Results:
- Identified 30 metabolites associated with HS and 49 with keloids.
- Telomere length positively correlated with scar types; PhenoAge negatively correlated.
- Eugenol sulfate and Phenylacetylglutamate were identified as key metabolites regulating scar formation via aging pathways.
Conclusions:
- Elucidated a causal network connecting metabolites, aging, and scar formation using genetic data.
- Highlighted Eugenol sulfate and Phenylacetylglutamate as promising targets for metabolic interventions.
- Provides a foundation for developing targeted therapies for hypertrophic scars and keloids.