Latent biochemical phenotypes delineate divergent health trajectories in older adults
Ageing heterogeneity hampers prevention and care. We used routine biochemical panels and unsupervised learning to identify latent phenotypes in community-dwelling older adults. In 1491 participants from the Toledo Study for Healthy Ageing (TSHA) with ~10-11 years of follow-up, 39 blood biomarkers were dimension-reduced and clustered, yielding three phenotypes: Healthy, Metabolic (subclinical dysmetabolism), and Haematological (low erythroid/renal profile). Phenotypes differed in functional capacity, frailty, and independence at baseline (all p < 0.05 after age/sex adjustment) and predicted long-term mortality (Metabolic women HR = 1.49, p = 0.016). Sex-specific analyses revealed distinct disease-trajectory patterns (e.g., hypertension in Metabolic women HR = 1.30, p = 0.005; thrombosis in Haematological men HR = 7.20, p = 0.018; syncope in Haematological women HR = 1.88, p = 0.009). Findings are partially replicated in a cohort of physically active older adults (EXERNET), supporting the generalizability of the Metabolic phenotype. Standard laboratory data, integrated through machine learning, capture ageing-relevant biology and stratify future risk without specialised assays, enabling low-cost, scalable precision prevention.
Authors
- Leocadio Rodríguez‐Mañas (ORCID: https://orcid.org/0000-0002-6551-1333)
- Carmen Ramírez‐Castillejo (ORCID: https://orcid.org/0000-0002-1877-3381)
- Francisco J. García‐García (ORCID: https://orcid.org/0000-0003-3690-6069)
- Raquel González‐Martos (ORCID: https://orcid.org/0000-0003-3340-1794)
- Amelia Guadalupe-Grau
- Ignacio Ara (ORCID: https://orcid.org/0000-0002-2854-6684)
- Luis M. Alegre
- Javier Galeano
- Irene Rodríguez-Gómez
Institutions
- Instituto de Salud Carlos III (ES)
- ProMedica Toledo Hospital (US)
- Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (ES)
- Hospital Universitario de Getafe (ES)
- Light Prescriptions Innovators (Spain) (ES)
- Servicio de Salud de Castilla La Mancha (ES)
- Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (ES)
- Complejo Hospitalario Universitario de Toledo (ES)
- European Telecommunications Standards Institute (FR)
- University of Castilla-La Mancha (ES)
- Universidad Politécnica de Madrid (ES)
Publication Details
- Journal
- npj Aging
- Published
- 2026-05-29
- DOI
- https://doi.org/10.1038/s41514-026-00415-4
- Primary Topic
- Health, Environment, Cognitive Aging
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable
- Comunidad de Madrid
- European Commission
- Ministerio de Economía y Competitividad
- Consejería de Sanidad de Castilla-La Mancha
- Junta de Comunidades de Castilla-La Mancha
- Instituto de Salud Carlos III