The multiomics blueprint of the individual with the most extreme lifespan
Extreme human lifespan, exemplified by supercentenarians, presents a paradox in understanding aging: despite advanced age, they maintain relatively good health. To investigate this duality, we have performed a high-throughput multiomics study of the world's oldest living person, interrogating her genome, transcriptome, metabolome, proteome, microbiome, and epigenome, comparing the results with larger matched cohorts. The emerging picture highlights different pathways attributed to each process: the record-breaking advanced age is manifested by telomere attrition, abnormal B cell population, and clonal hematopoiesis, whereas absence of typical age-associated diseases is associated with rare European-population genetic variants, low inflammation levels, a rejuvenated bacteriome, and a younger epigenome. These findings provide a fresh look at human aging biology, suggesting biomarkers for healthy aging, and potential strategies to increase life expectancy. The extrapolation of our results to the general population will require larger cohorts and longitudinal prospective studies to design potential anti-aging interventions.
Authors
- Núria Amigó (ORCID: https://orcid.org/0000-0002-0116-9145)
- Toni Gabaldón (ORCID: https://orcid.org/0000-0003-0019-1735)
- Aleix Noguera‐Castells (ORCID: https://orcid.org/0000-0001-7436-6513)
- Manel Esteller (ORCID: https://orcid.org/0000-0003-4490-6093)
- Claudia Vasallo (ORCID: https://orcid.org/0000-0002-0043-0882)
- Xavier Aldeguer (ORCID: https://orcid.org/0000-0003-4597-8339)
- Lauro Sumoy (ORCID: https://orcid.org/0000-0003-0005-4618)
- Pamela Acha (ORCID: https://orcid.org/0000-0002-4528-1219)
- Ignacio Campillo‐Marcos (ORCID: https://orcid.org/0000-0002-7657-7127)
- Mauricio Moldes (ORCID: https://orcid.org/0000-0001-5455-7769)
- Carles Arribas
- Mar Mallo (ORCID: https://orcid.org/0000-0001-7741-498X)
- Caterina Mata (ORCID: https://orcid.org/0000-0001-9403-7434)
- Marta Casado-Peláez (ORCID: https://orcid.org/0000-0002-8428-8384)
- Óscar Yanes (ORCID: https://orcid.org/0000-0003-3695-7157)
- Isabel Granada (ORCID: https://orcid.org/0000-0002-4275-0104)
- Fernando Setién (ORCID: https://orcid.org/0000-0002-4061-4635)
- Fabio Barteri (ORCID: https://orcid.org/0000-0003-0844-512X)
- Raúl Sánchez-Vazquez (ORCID: https://orcid.org/0000-0001-6653-7386)
- Raquel Pluvinet (ORCID: https://orcid.org/0000-0002-4955-8238)
- Gerardo Ferrer (ORCID: https://orcid.org/0000-0002-4084-6815)
- Alberto Bueno-Costa (ORCID: https://orcid.org/0000-0001-8700-2540)
- Pablo Torné (ORCID: https://orcid.org/0000-0001-8700-6058)
- Salvador Macip (ORCID: https://orcid.org/0000-0003-1963-8840)
- Arcadi Navarro (ORCID: https://orcid.org/0000-0003-2162-8246)
- Marc Llirós (ORCID: https://orcid.org/0000-0001-8456-4230)
- Donald J. L. Jones (ORCID: https://orcid.org/0000-0001-6583-870X)
- Hafid Laayouni (ORCID: https://orcid.org/0000-0003-1297-5078)
- Paula Martínez (ORCID: https://orcid.org/0000-0002-4655-5672)
- Elisabetta Mereu (ORCID: https://orcid.org/0000-0001-6101-8472)
- Sara Samino (ORCID: https://orcid.org/0000-0001-8371-679X)
- Verónica Dávalos (ORCID: https://orcid.org/0000-0003-4077-5137)
- Aleix Lluansí (ORCID: https://orcid.org/0000-0002-2328-6780)
- Montse Guardiola (ORCID: https://orcid.org/0000-0002-9696-7384)
- Robert Carreras‐Torres (ORCID: https://orcid.org/0000-0002-2925-734X)
- Gerard Muntané (ORCID: https://orcid.org/0000-0003-1541-8365)
- Marta Massip‐Salcedo (ORCID: https://orcid.org/0000-0002-6302-3280)
- Françesc Solé (ORCID: https://orcid.org/0000-0002-3251-2161)
- Thong Huy Cao (ORCID: https://orcid.org/0000-0002-6559-0836)
- Josep Ribalta (ORCID: https://orcid.org/0000-0002-8879-4719)
- Marı́a A. Blasco (ORCID: https://orcid.org/0000-0002-4211-233X)
- L. J. Garcia‐Gil (ORCID: https://orcid.org/0000-0002-5064-8361)
- Carlos A. García‐Prieto (ORCID: https://orcid.org/0000-0001-5021-6916)
- Eloy Santos-Pujol (ORCID: https://orcid.org/0000-0002-7788-6562)
- Eva Crespo-García
- Julia Rius-Bonet (ORCID: https://orcid.org/0009-0002-3787-6914)
- Carlos Quero-Dotor (ORCID: https://orcid.org/0000-0002-3951-2287)
- Carolina de la Torre (ORCID: https://orcid.org/0000-0001-9363-291X)
- Paulene A. Quinn
- Francisco Villavicencio
- Natalie S. Coles
- Sara Peregrina
- Meritxell Pujolassos
- Jose Oviedo (ORCID: https://orcid.org/0009-0007-8248-2208)
- Bernardo Lemos
- Marta Torrubiano
- Kamal A. Khidir
- Eva Brigos-Barril (ORCID: https://orcid.org/0000-0002-0043-8067)
Institutions
- Universitat de Vic - Universitat Central de Catalunya (ES)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- APLA Health (US)
- University of Arizona (US)
- Universitat Oberta de Catalunya (ES)
- University of Leicester (GB)
- Barcelona Supercomputing Center (ES)
- Instituto de Salud Carlos III (ES)
- Institut Pere Mata (ES)
- Glenfield Hospital (GB)
- University Hospitals of Leicester NHS Trust (GB)
- Josep Carreras Leukaemia Research Institute (ES)
- Spanish National Cancer Research Centre (ES)
- Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (ES)
- Institut de Recerca Biomèdica Catalunya Sud (ES)
- Institut Català d'Oncologia (ES)
- Pasqual Maragall Foundation (ES)
- Institut d'Investigació Biomèdica de Girona (ES)
- Hospital Sant Pau i Santa Tecla (ES)
- Institute for Research in Biomedicine (ES)
- Institut de Biologia Evolutiva (ES)
- Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (ES)
- Centre for Genomic Regulation (ES)
- Molecular Oncology (United States) (US)
- Hospital Universitari de Girona Doctor Josep Trueta (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Barcelona School of Economics (ES)
- Universitat Politècnica de Catalunya (ES)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-09-25
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102368
- Citations
- 10
- Primary Topic
- Genetics, Aging, and Longevity in Model Organisms
- Type
- article
- Field-Weighted Citation Impact
- 9.53