The multiomics blueprint of the individual with the most extreme lifespan
Por:
Santos-Pujol E, Noguera-Castells A, Casado-Pelaez M, García-Prieto CA, Vasallo C, Campillo-Marcos I, Quero-Dotor C, Crespo-García E, Bueno-Costa A, Setién F, Ferrer G, Davalos V, Mereu E, Pluvinet R, Arribas C, Torre C, Villavicencio F, Sumoy L, Granada I, Coles NS, Acha P, Solé F, Mallo M, Mata C, Peregrina S, Gabaldón T, Llirós M, Pujolassos M, Carreras-Torres R, Lluansí A, García-Gil LJ, Aldeguer X, Samino S, Torné P, Ribalta J, Guardiola M, Amigó N, Yanes O, Martínez P, Sánchez-Vázquez R, Blasco MA, Oviedo J, Lemos B, Rius-Bonet J, Torrubiano M, Massip-Salcedo M, Khidir KA, Cao TH, Quinn PA, Jones DJL, Macip S, Brigos-Barril E, Moldes M, Barteri F, Muntané G, Laayouni H, Navarro A and Esteller M
Publicada:
21 oct 2025
Ahead of Print:
1 oct 2025
Resumen:
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 afresh 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.
Filiaciones:
Santos-Pujol E:
Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Noguera-Castells A:
Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Department of Biosciences, Faculty of Science, Technology and Engineering, University of Vic - Central University of Catalonia (UVic-UCC), Vic, Barcelona, Catalonia, Spain
Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain
Casado-Pelaez M:
Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
García-Prieto CA:
Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona, Catalonia, Spain
Vasallo C:
BarcelonaBeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Catalonia, Spain
Institute of Evolutionary Biology (IBE, UPF-CSIC), Department of Medicine and Life, Barcelona, Catalonia, Spain
Campillo-Marcos I:
Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain
Quero-Dotor C:
Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain
Crespo-García E:
Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Bueno-Costa A:
Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Setién F:
Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Ferrer G:
Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain
Davalos V:
Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain
Mereu E:
Cellular Systems Genomics Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Pluvinet R:
Genomics Unit, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
High Content Genomics and Bioinformatics (HCGB)-Germans Trias I Pujol Research Institute (IGTP), Badalona, Barcelona, Catalonia, Spain
Arribas C:
Genomics Unit, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Torre C:
Proteomics Unit, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Villavicencio F:
Department of Economic, Financial and Actuarial Mathematics, University of Barcelona, Barcelona, Catalonia, Spain
Sumoy L:
High Content Genomics and Bioinformatics (HCGB)-Germans Trias I Pujol Research Institute (IGTP), Badalona, Barcelona, Catalonia, Spain
Granada I:
Hematology Department, Hospital Germans Trias i Pujol, Institut Català d'Oncologia, Josep Carreras Leukaemia Research Institute, Barcelona, Spain
Coles NS:
Los Angeles Gerontology Research Group, Los Angeles, CA, USA
Acha P:
Myelodysplastic Syndromes Research Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Solé F:
Myelodysplastic Syndromes Research Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Mallo M:
Myelodysplastic Syndromes Research Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Microarrays Unit, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Mata C:
Single Cell Unit, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Peregrina S:
Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona, Catalonia, Spain
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain
Gabaldón T:
Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona, Catalonia, Spain
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain
Institució Catalana de Recerca i Estudis Avançats (ICREA) and Universitat Pompeu Fabra, Barcelona, Catalonia, Spain
CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
Llirós M:
Bioinformatics and Bioimaging (BI-SQUARED) Research Group, Biosciences Department, Faculty of Science, Technology and Engineering, Universitat de Vic - Universitat Central de Catalunya, Vic, Catalunya, Spain
Pujolassos M:
Bioinformatics and Bioimaging (BI-SQUARED) Research Group, Biosciences Department, Faculty of Science, Technology and Engineering, Universitat de Vic - Universitat Central de Catalunya, Vic, Catalunya, Spain
Carreras-Torres R:
Digestive Diseases and Microbiota Group, Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI), Girona, Catalonia, Spain
Lluansí A:
Digestive Diseases and Microbiota Group, Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI), Girona, Catalonia, Spain
Infectious diseases and Microbiome Unit, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Catalunya, Spain
García-Gil LJ:
Digestive Diseases and Microbiota Group, Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI), Girona, Catalonia, Spain
Biology Department, Universitat de Girona, Girona, Catalunya, Spain
Aldeguer X:
Digestive Diseases and Microbiota Group, Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta (IDIBGI), Girona, Catalonia, Spain
Digestive Service, Hospital Universitari de Girona Dr Josep Trueta, Girona, Catalunya, Spain
Samino S:
Biosfer Teslab, 43201 Reus, Tarragona, Spain
Torné P:
Biosfer Teslab, 43201 Reus, Tarragona, Spain
Ribalta J:
Universitat Rovira i Virgili, Department of Basic Medical Sciences, Reus, Spain
Institut d'Investigació Sanitària Pere Virgili, Reus, Spain
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
Guardiola M:
Universitat Rovira i Virgili, Department of Basic Medical Sciences, Reus, Spain
Institut d'Investigació Sanitària Pere Virgili, Reus, Spain
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
Amigó N:
Biosfer Teslab, 43201 Reus, Tarragona, Spain
Universitat Rovira i Virgili, Department of Basic Medical Sciences, Reus, Spain
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
Yanes O:
Institut d'Investigació Sanitària Pere Virgili, Reus, Spain
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
Universitat Rovira i Virgili, Department of Electronic Engineering, Tarragona, Spain
Martínez P:
Telomeres and Telomerase Group - Fundación Humanismo y Ciencia, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain
Sánchez-Vázquez R:
Telomeres and Telomerase Group - Fundación Humanismo y Ciencia, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain
Blasco MA:
Telomeres and Telomerase Group - Fundación Humanismo y Ciencia, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain
Oviedo J:
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Department of Pharmacology and Toxicology, R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, AZ, USA
Lemos B:
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Department of Pharmacology and Toxicology, R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, AZ, USA
Coit Center for Longevity and Neurotherapeutics, The University of Arizona, Tucson, AZ, USA
Rius-Bonet J:
BarcelonaBeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Catalonia, Spain
epi4health, Faculty of Health Sciences, Universitat Oberta de Catalunya, 08018 Barcelona, Catalonia, Spain
Torrubiano M:
epi4health, Faculty of Health Sciences, Universitat Oberta de Catalunya, 08018 Barcelona, Catalonia, Spain
Massip-Salcedo M:
BarcelonaBeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Catalonia, Spain
epi4health, Faculty of Health Sciences, Universitat Oberta de Catalunya, 08018 Barcelona, Catalonia, Spain
Khidir KA:
Mechanisms of Cancer and Aging Laboratory, Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, UK
University of Raparin, Kurdistan Region, Iraq
Cao TH:
Department of Cardiovascular Sciences, College of Life Sciences, University of Leicester, Leicester LE1 7RH, UK
National Institute for Health and Care Research Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester LE3 9QP, UK
Leicester van Geest MultiOMICS Facility, University of Leicester, Leicester LE1 7RH, UK
Quinn PA:
Department of Cardiovascular Sciences, College of Life Sciences, University of Leicester, Leicester LE1 7RH, UK
Leicester van Geest MultiOMICS Facility, University of Leicester, Leicester LE1 7RH, UK
Jones DJL:
Leicester van Geest MultiOMICS Facility, University of Leicester, Leicester LE1 7RH, UK
Leicester Cancer Research Centre, University Hospitals of Leicester NHS Trust, Leicester Royal Infirmary, University of Leicester, Leicester LE1 5WW, UK
Macip S:
BarcelonaBeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Catalonia, Spain
epi4health, Faculty of Health Sciences, Universitat Oberta de Catalunya, 08018 Barcelona, Catalonia, Spain
Mechanisms of Cancer and Aging Laboratory, Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, UK
Brigos-Barril E:
Institute of Evolutionary Biology (IBE, UPF-CSIC), Department of Medicine and Life, Barcelona, Catalonia, Spain
Department of Medicine and Life Sciences, Universitat Pompeu Fabra, PRBB, Barcelona, Spain
Moldes M:
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain
Barteri F:
BarcelonaBeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Catalonia, Spain
Muntané G:
Department of Medicine and Life Sciences, Universitat Pompeu Fabra, PRBB, Barcelona, Spain
Hospital Universitari Institut Pere Mata (HUIPM), Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili (URV), Catalonia, Spain
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Laayouni H:
BarcelonaBeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Catalonia, Spain
Department of Medicine and Life Sciences, Universitat Pompeu Fabra, PRBB, Barcelona, Spain
Navarro A:
BarcelonaBeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Catalonia, Spain
Institute of Evolutionary Biology (IBE, UPF-CSIC), Department of Medicine and Life, Barcelona, Catalonia, Spain
Institució Catalana de Recerca i Estudis Avançats (ICREA) and Universitat Pompeu Fabra, Barcelona, Catalonia, Spain
Department of Medicine and Life Sciences, Universitat Pompeu Fabra, PRBB, Barcelona, Spain
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain
Esteller M:
Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain
Institució Catalana de Recerca i Estudis Avançats (ICREA) and Universitat Pompeu Fabra, Barcelona, Catalonia, Spain
Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Catalonia, Spain
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