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. 2025 Sep 24:102368.
doi: 10.1016/j.xcrm.2025.102368. Online ahead of print.

The multiomics blueprint of the individual with the most extreme lifespan

Eloy Santos-Pujol  1 , Aleix Noguera-Castells  2 , Marta Casado-Pelaez  1 , Carlos A García-Prieto  3 , Claudia Vasallo  4 , Ignacio Campillo-Marcos  5 , Carlos Quero-Dotor  5 , Eva Crespo-García  1 , Alberto Bueno-Costa  1 , Fernando Setién  1 , Gerardo Ferrer  5 , Veronica Davalos  5 , Elisabetta Mereu  6 , Raquel Pluvinet  7 , Carles Arribas  8 , Carolina de la Torre  9 , Francisco Villavicencio  10 , Lauro Sumoy  11 , Isabel Granada  12 , Natalie S Coles  13 , Pamela Acha  14 , Francesc Solé  14 , Mar Mallo  15 , Caterina Mata  16 , Sara Peregrina  17 , Toni Gabaldón  18 , Marc Llirós  19 , Meritxell Pujolassos  19 , Robert Carreras-Torres  20 , Aleix Lluansí  21 , Librado Jesús García-Gil  22 , Xavier Aldeguer  23 , Sara Samino  24 , Pol Torné  24 , Josep Ribalta  25 , Montse Guardiola  25 , Núria Amigó  26 , Oscar Yanes  27 , Paula Martínez  28 , Raúl Sánchez-Vázquez  28 , Maria A Blasco  28 , Jose Oviedo  29 , Bernardo Lemos  30 , Julia Rius-Bonet  31 , Marta Torrubiano  32 , Marta Massip-Salcedo  31 , Kamal A Khidir  33 , Thong Huy Cao  34 , Paulene A Quinn  35 , Donald J L Jones  36 , Salvador Macip  37 , Eva Brigos-Barril  38 , Mauricio Moldes  39 , Fabio Barteri  40 , Gerard Muntané  41 , Hafid Laayouni  42 , Arcadi Navarro  43 , Manel Esteller  44
Affiliations
Free article

The multiomics blueprint of the individual with the most extreme lifespan

Eloy Santos-Pujol et al. Cell Rep Med. .
Free article

Abstract

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.

Keywords: aging; epigenetics; genetics; microbiome; supercentenarian.

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Conflict of interest statement

Declaration of interests M.E. declares past grants from Ferrer International and Incyte and personal fees from Quimatryx and Eucerin, outside of the submitted work.

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