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, interrogati...

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Autores: Santos-Pujol, Eloy, Vasallo, Claudia, Gabaldón Estevan, Juan Antonio, 1973-, Brigos-Barril, Eva, Moldes, Mauricio, Muntané, Gerard, Laayouni, Hafid, 1968-, Navarro i Cuartiellas, Arcadi, 1969-, Esteller, Manel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:dnet:rdupf_______::01abb6cfb6981a7e3287eef1c59fd9fe
Acceso en línea:https://hdl.handle.net/10230/72822
http://dx.doi.org/10.1016/j.xcrm.2025.102368
Access Level:acceso abierto
Palabra clave:Aging
Supercentenarian
Genetics
Epigenetics
Microbiome
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dc.title.none.fl_str_mv The multiomics blueprint of the individual with the most extreme lifespan
title The multiomics blueprint of the individual with the most extreme lifespan
spellingShingle The multiomics blueprint of the individual with the most extreme lifespan
Santos-Pujol, Eloy
Aging
Supercentenarian
Genetics
Epigenetics
Microbiome
title_short The multiomics blueprint of the individual with the most extreme lifespan
title_full The multiomics blueprint of the individual with the most extreme lifespan
title_fullStr The multiomics blueprint of the individual with the most extreme lifespan
title_full_unstemmed The multiomics blueprint of the individual with the most extreme lifespan
title_sort The multiomics blueprint of the individual with the most extreme lifespan
dc.creator.none.fl_str_mv Santos-Pujol, Eloy
Vasallo, Claudia
Gabaldón Estevan, Juan Antonio, 1973-
Brigos-Barril, Eva
Moldes, Mauricio
Muntané, Gerard
Laayouni, Hafid, 1968-
Navarro i Cuartiellas, Arcadi, 1969-
Esteller, Manel
author Santos-Pujol, Eloy
author_facet Santos-Pujol, Eloy
Vasallo, Claudia
Gabaldón Estevan, Juan Antonio, 1973-
Brigos-Barril, Eva
Moldes, Mauricio
Muntané, Gerard
Laayouni, Hafid, 1968-
Navarro i Cuartiellas, Arcadi, 1969-
Esteller, Manel
author_role author
author2 Vasallo, Claudia
Gabaldón Estevan, Juan Antonio, 1973-
Brigos-Barril, Eva
Moldes, Mauricio
Muntané, Gerard
Laayouni, Hafid, 1968-
Navarro i Cuartiellas, Arcadi, 1969-
Esteller, Manel
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Aging
Supercentenarian
Genetics
Epigenetics
Microbiome
topic Aging
Supercentenarian
Genetics
Epigenetics
Microbiome
description 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.
publishDate 2025
dc.date.none.fl_str_mv 2025
2026
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/10230/72822
http://dx.doi.org/10.1016/j.xcrm.2025.102368
url https://hdl.handle.net/10230/72822
http://dx.doi.org/10.1016/j.xcrm.2025.102368
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cell Reports Medicine. 2025;6(10):102368
info:eu-repo/grantAgreement/EC/H2020/882385
info:eu-repo/grantAgreement/EC/HE/101136622
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
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spelling The multiomics blueprint of the individual with the most extreme lifespanSantos-Pujol, EloyVasallo, ClaudiaGabaldón Estevan, Juan Antonio, 1973-Brigos-Barril, EvaMoldes, MauricioMuntané, GerardLaayouni, Hafid, 1968-Navarro i Cuartiellas, Arcadi, 1969-Esteller, ManelAgingSupercentenarianGeneticsEpigeneticsMicrobiomeExtreme 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.We thank Yoana Veselinova for the drawing of the graphical abstract. Research in the M.E. group is funded by the CERCA Programme/Generalitat de Catalunya (MCIN/AEI/10.13039/501100011033/); the European Regional Development Fund, "A way to make Europe" ERDF (Project PID2021-125282OB-I00 and PID2024-159192OB-I00); Departament de Recerca i Universitats/Generalitat de Catalunya (2021 SGR 01494); European Union under THRIVE grant agreement no. 101136622; "La Caixa" Research Foundation; and the Cellex Foundation (CEL007). E.S.-P. is a fellow of the Spanish Ministry of Science, Innovation and Universities, under FPI contract no. PRE2022-105015. G.F. is a recipient of Ayuda Investigador AECC 2023 (INVES234765FERR), Fundación Científica AECC. C.Q.-D. is a fellow of the Spanish Ministry of Science, Innovation and Universities, under FPU contract no. FPU22/01655. E.M.'s work in this publication was supported by the Ramón y Cajal fellowship RYC2021-032359-I, funded by the Spanish Ministry of Science and the Catalan Government. Agency for Management of University and Research Grants (AGAUR, 2021 SGR 01586). Research in the A.N. group is supported by the I+D+i project PID2021-127792NB-I00, funded by MCIN/AEI/10.13039/501100011033 (FEDER Una manera de hacer Europa), and "Unidad de Excelencia María de Maeztu", funded by the AEI (CEX2018-000792-M) and Departament de Recerca i Universitats de la Generalitat de Catalunya (GRC 2021 SGR 0467). Research in the R.C.-T. group is funded by the Departament de Recerca i Universitats/Generalitat de Catalunya (2021 SGR 01366). Research in the S.M. group was supported by the Instituto de Salud Carlos III (PI20/00328) and the M. C. Andreu Memorial Fund. J. R.-B. was supported by a doctoral grant from the Universitat Oberta de Catalunya. Research in the M.A.B. laboratory is funded by the European Union, project ERC-AvG Shelterins (GA 882385), Horizon 2020 Programme. The mass spectrometry work was supported by the John and Lucille Van Geest Foundation and the National Institute for Health and Care Research Leicester Biomedical Research Centre. M.E. is an ICREA Research Professor. Special thanks are given to personnel taking care of M116 and to all of the biobank technicians involved in and contributing to keeping samples and procedures for the current research, with special mention to Gerard Pardo Albiñana.Elsevier2026202620252026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/10230/72822http://dx.doi.org/10.1016/j.xcrm.2025.102368reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésCell Reports Medicine. 2025;6(10):102368info:eu-repo/grantAgreement/EC/H2020/882385info:eu-repo/grantAgreement/EC/HE/101136622© 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:dnet:rdupf_______::01abb6cfb6981a7e3287eef1c59fd9fe2026-06-12T07:21:37Z
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