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Article Abstract

Background: As humans age at different rates, physical appearance can yield insights into biological age and physiological health more reliably than chronological age. In medicine, however, appearance is incorporated into medical judgements in a subjective and non-standardised way. In this study, we aimed to develop and validate FaceAge, a deep learning system to estimate biological age from easily obtainable and low-cost face photographs.

Methods: FaceAge was trained on data from 58 851 presumed healthy individuals aged 60 years or older: 56 304 individuals from the IMDb-Wiki dataset (training) and 2547 from the UTKFace dataset (initial validation). Clinical utility was evaluated on data from 6196 patients with cancer diagnoses from two institutions in the Netherlands and the USA: the MAASTRO, Harvard Thoracic, and Harvard Palliative cohorts FaceAge estimates in these cancer cohorts were compared with a non-cancerous reference cohort of 535 individuals. To assess the prognostic relevance of FaceAge, we performed Kaplan-Meier survival analysis and Cox modelling, adjusting for several clinical covariates. We also assessed the performance of FaceAge in patients with metastatic cancer receiving palliative treatment at the end of life by incorporating FaceAge into clinical prediction models. To evaluate whether FaceAge has the potential to be a biomarker for molecular ageing, we performed a gene-based analysis to assess its association with senescence genes.

Findings: FaceAge showed significant independent prognostic performance in various cancer types and stages. Looking older was correlated with worse overall survival (after adjusting for covariates per-decade hazard ratio [HR] 1·151, p=0·013 in a pan-cancer cohort of n=4906; 1·148, p=0·011 in a thoracic cohort of n=573; and 1·117, p=0·021 in a palliative cohort of n=717). We found that, on average, patients with cancer looked older than their chronological age (mean increase of 4·79 years with respect to non-cancerous reference cohort, p<0·0001). We found that FaceAge can improve physicians' survival predictions in patients with incurable cancer receiving palliative treatments (from area under the curve 0·74 [95% CI 0·70-0·78] to 0·8 [0·76-0·83]; p<0·0001), highlighting the clinical use of the algorithm to support end-of-life decision making. FaceAge was also significantly associated with molecular mechanisms of senescence through gene analysis, whereas age was not.

Interpretation: Our results suggest that a deep learning model can estimate biological age from face photographs and thereby enhance survival prediction in patients with cancer. Further research, including validation in larger cohorts, is needed to verify these findings in patients with cancer and to establish whether the findings extend to patients with other diseases. Subject to further testing and validation, approaches such as FaceAge could be used to translate a patient's visual appearance into objective, quantitative, and clinically valuable measures.

Funding: US National Institutes of Health and EU European Research Council.

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http://dx.doi.org/10.1016/j.landig.2025.03.002DOI Listing

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