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Genetically Proxied Biological Aging and Risk of Hypertrophic Scar/Keloid-Coded Phenotypes: An Exploratory Two-Sample
Zequn Chen1, Bingmin Li2, Rui Gao3
1The Third Ward of Department of Burn, Senior Department of Burns and Plastic Surgery, The Fourth Medical Center of Chinese PLA General Hospital, Beijing, People's Republic of China.
Clinical, Cosmetic and Investigational Dermatology
|July 19, 2026
Summary
Investigating biological aging and hypertrophic scars (HS), this study found that faster epigenetic aging may be linked to a reduced risk of HS. These findings suggest a novel connection between aging processes and scar development.
Area of Science:
- Genetics
- Aging Research
- Dermatology
Background:
- Hypertrophic scars (HS) are common fibroproliferative disorders affecting younger individuals.
- Understanding the underlying causes of HS is crucial for developing effective treatments.
- Biological aging indicators are increasingly recognized as potential factors influencing various health outcomes.
Purpose of the Study:
- To investigate potential causal associations between genetically proxied biological aging indicators and the risk of hypertrophic scars (HS).
- To utilize a two-sample Mendelian randomization (MR) approach to assess these relationships.
- To explore the interplay between aging processes and scar formation.
Main Methods:
- Employed genome-wide association studies (GWAS) data for two-sample Mendelian randomization (MR).
- Analyzed epigenetic clocks (e.g., IEAA, PhenoAge), telomere length, and macroscopic aging indicators.
- Conducted primary inverse-variance weighted MR with sensitivity analyses (MR-Egger, weighted median, weighted mode) and multivariable MR, validated in independent cohorts.
Main Results:
- Genetically predicted higher IEAA and PhenoAge were nominally associated with a decreased risk of HS (OR=0.926, P=0.004; OR=0.911, P=0.011, respectively).
- The PhenoAge association was replicated in an independent cohort (OR=0.91, P=0.0059).
- Associations did not remain significant after False Discovery Rate correction; no significant pleiotropy was detected.
Conclusions:
- Exploratory evidence suggests genetically proxied faster epigenetic aging may be nominally associated with a reduced risk of HS.
- These findings propose novel hypotheses regarding the complex interplay between aging processes and scar formation.
- Further research is warranted to confirm these associations and elucidate underlying mechanisms.