Thymic health consequences in adults.

Authors

Bernatz S, Prudente V, Pai S, Attermann AK, Cao Y, Chen J, Lyass A, Foldyna B, Nürnberg L, Bressem K, Abbosh C, Swanton C, Jamal-Hanjani M, Lu MT, Murabito JM, Lunetta KL, Birkbak NJ, Aerts HJWL

Affiliations

• Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham & Harvard Medical School, Boston, MA, USA.
• Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
• Department of Mathematics and Statistics, Boston University, Boston, MA, USA.
• Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
• Framingham Heart Study, National Heart, Lung and Blood Institute and Boston University Chobanian and Avedisian School of Medicine, Framingham, MA, USA.
• Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
• Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham & Harvard Medical School, Boston, MA, USA. haerts@bwh.harvard.edu.

Abstract

The thymus is essential for establishing T cell diversity early in life, but undergoes profound involution with age and has therefore traditionally been regarded as largely nonfunctional in adults^1,2. Here we propose that preserving thymic functionality is integral to adult health and longevity. We developed a deep learning framework to quantify thymic health from routine radiographic images and evaluated its association with longevity and risk of major age-associated diseases in two large prospective cohorts of asymptomatic adults: the National Lung Screening Trial (n = 25,031) and the Framingham Heart Study (n = 2,581). In both cohorts, thymic health varied markedly across the population. In the National Lung Screening Trial, higher thymic health was consistently associated with lower all-cause mortality, reduced lung cancer incidence and lower cardiovascular mortality over 12 years of follow-up after adjustment for age, sex, smoking and comorbidities. In the independent Framingham Heart Study cohort, higher thymic health was significantly associated with reduced cardiovascular mortality, independent of age, sex and smoking. Thymic health was further linked to systemic inflammation and metabolic dysregulation, and associated with modifiable lifestyle factors including smoking, obesity and physical activity. Together, these findings reposition the thymus as a central regulator of immune-mediated ageing and disease susceptibility in adulthood, highlighting its potential as a target for preventive and regenerative strategies to promote healthy ageing and longevity.