The multiomics blueprint of the individual with the most extreme lifespan
Eloy Santos-Pujol, Aleix Noguera‐Castells, Marta Casado-Peláez, Carlos A. García‐Prieto, Claudia Vasallo, Ignacio Campillo‐Marcos, Carlos Quero-Dotor, Eva Crespo-García, Alberto Bueno-Costa, Fernando Setién, Gerardo Ferrer, Verónica Dávalos, Elisabetta Mereu, Raquel Pluvinet, Carles Arribas, Carolina de la Torre, Francisco Villavicencio, Lauro Sumoy, Isabel Granada, Natalie S. Coles, Pamela Acha, Françesc Solé, Mar Mallo, Caterina Mata, Sara Peregrina, Toni Gabaldón, Marc Llirós, Meritxell Pujolassos, Robert Carreras‐Torres, Aleix Lluansí, L. J. Garcia‐Gil, Xavier Aldeguer, Sara Samino, Pol Torné, Josep Ribalta, Montse Guardiola, Núria Amigó, Óscar Yanes, Paula Martínez, Raúl Sánchez-Vazquez, Marı́a A. Blasco, Jose Oviedo, Bernardo Lemos, Julia Rius-Bonet, Marta Torrubiano, Marta Massip‐Salcedo, Kamal A. Khidir, Thong Huy Cao, Paulene A. Quinn, Donald J. L. Jones, Salvador Macip, Eva Brigos-Barril, Mauricio Moldes, Fabio Barteri, Gerard Muntané, Hafid Laayouni, Arcadi Navarro, Manel Esteller
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.