A Survey on Forensic Age Estimation through Dna Methylation: Recent Progress and Future Directions Towards Legal Age Estimation

Abstract

[Abstract]: DNA methylation (DNAm) has emerged as one of the most promising molecular biomarkers for age estimation (AE), offering a powerful complement to traditional anthropological and radiological methods. Its potential spans forensic, biomedical, and humanitarian domains, particularly in the identification of deceased individuals and the estimation of legal age in living persons. Despite its rapid development, the forensic implementation of DNAm-based AE models remains challenged by issues of validation, dataset diversity, and tissue-specific variability.

This survey provides an up-to-date overview of DNAm-based AE models developed between 2019 and 2025. We catalogued and analyzed published models according to their data origin, tissue type, methylation quantification method, and mathematical approach. We also distinguish between models designed to estimate chronological age in living individuals and those focused on age-at-death estimation in deceased persons. Our analysis highlights trends toward tissue-specific model optimization, targeted approaches with a small number of markers, and the integration of machine learning to improve predictive performance.

Special attention is given to the development of pediatric and young-adult epigenetic clocks tailored to the estimation of legal age, an area with growing societal and humanitarian relevance, particularly in migration and child protection contexts. By identifying the main methodological advances, limitations, and challenges, this review outlines a roadmap for the next generation of DNAm-based AE models, emphasizing the need for standardized validation protocols, increased population diversity, and interdisciplinary approaches that integrate molecular, radiological, and computational tools.