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 h...

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Authors: Santos-Pujol, Eloy, Noguera-Castells, Aleix, Casado-Pelaez, Marta, García-Prieto, Carlos A, Vasallo, Claudia, Campillo-Marcos, Ignacio, Quero-Dotor, Carlos, Crespo-García, Eva, Bueno-Costa, Alberto, Setién, Fernando, Ferrer, Gerardo, Davalos, Veronica, Mereu, Elisabetta, Pluvinet, Raquel, Arribas, Carles, Torre, Carolina de la, Villavicencio, Francisco, Sumoy, Lauro, Granada, Isabel, Coles, Natalie S, Acha, Pamela, Solé, Francesc, Mallo, Mar, Mata, Caterina, Peregrina, Sara, Gabaldón, Toni, Llirós, Marc, Pujolassos, Meritxell, Carreras-Torres, Robert, Lluansí, Aleix, García-Gil, Librado Jesús, Aldeguer, Xavier, Samino, Sara, Torné, Pol, Ribalta, Josep, Guardiola, Montse, Amigó, Núria, Yanes, Oscar, Martínez, Paula, Sánchez-Vázquez, Raúl, Blasco, Maria A, Oviedo, Jose, Lemos, Bernardo, Rius-Bonet, Julia, Torrubiano, Marta, Massip-Salcedo, Marta, Khidir, Kamal A, Cao, Thong Huy, Quinn, Paulene A, Jones, Donald J L, Macip, Salvador, Brigos-Barril, Eva, Moldes, Mauricio, Barteri, Fabio, Muntané, Gerard, Laayouni, Hafid, Navarro, Arcadi, Esteller, Manel
Format: article
Status:Published version
Publication Date:2025
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:dnet:digitalcsic_::4c58156fb06cbd3abd89efa2dc65356f
Online Access:http://hdl.handle.net/10261/427626
https://api.elsevier.com/content/abstract/scopus_id/105019821039
Access Level:Open access
Keyword:Aging
Epigenetics
Genetics
Microbiome
Supercentenarian
Description
Summary: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.

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