2026-04-14T04:31:35Zhttps://recercat.cat/oai/request

oai:recercat.cat:10459.1/4671172025-09-15T18:27:24Zcom_2072_3622col_2072_479130

Phenotypic upregulation of hexocylceramides and ether-linked phosphocholines as markers of human extreme longevity Fernández Bernal, Anna Sol, Joaquim Galo-Licona, José Daniel Mota Martorell, Natàlia Mas-Bargues, Cristina Belenguer-Varea, Ángel Obis Monné, Èlia Viña Ribes, José Borrás, Consuelo Jové Font, Mariona Pamplona Gras, Reinald Centenarians Cententarians' offspring Ether lipids Extreme longevity Hexocylceramides Lipidomics Centenarians and their relatives possess a notable survival advantage, with higher longevity and reduced susceptibility to major age-related diseases. To date, characteristic omics profiles of centenarians have been described, demonstrating that these individuals with exceptional longevity regulate their metabolism to adapt and incorporate more resilient biomolecules into their cells. Among these adaptations, the lipidomic profile stands out. However, it has not yet been determined whether this lipidomic profile is specific to centenarians or is the consequence of extreme longevity genetics and is also present in centenarians' offspring. This distinction is crucial for defining potential therapeutic targets that could help delay the aging process and associated pathologies. We applied mass-spectrometry-based techniques to quantify 569 lipid species in plasma samples from 39 centenarians, 63 centenarians' offspring, and 69 noncentenarians' offspring without familial connections. Based on this profile, we calculated different indexes to characterize the functional and structural properties of plasma lipidome. Our findings demonstrate that extreme longevity genetics (centenarians and centenarians' offspring) determines a specific lipidomic signature characterized by (i) an enrichment of hexosylceramides, (ii) a decrease of specific species of ceramides and sulfatides, (iii) a global increase of ether-PC and ether-LPC, and (iv) changes in the fluidity and diversity of specific lipid classes. We point out the conversion of ceramides to hexosylceramides and the maintenance of the levels of the ether-linked PC as a phenotypic trait to guarantee extreme longevity. We propose that this molecular signature is the result of an intrinsic adaptive program that preserves protective mechanisms and cellular identity. Ministerio de Ciencia y Tecnología, Grant/Award Number: PID2020-113839RB-I00 and PID2023-152233OB-I00; Diputació de Lleida, Grant/Award Number:PP10605-PIRS2021 and PP10845-PIRS2023; Instituto de Salud Carlos III,Grant/Award Number: AC20/00026,CB16/10/00435 (CIBERFES) and PI24/01431; Conselleria d'Educació,Investigació, Cultura i Esport, Grant/Award Number: CIAICO/2022/190; Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya, Grant/Award Number: 2021SGR00990; Horizon 2020 Framework Programme, Grant/Award Number: 696295 and 825546 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113839RB-I00/ES/EFECTO DEL TRATAMIENTO CON VESICULAS EXTRACELULARES DE CELULAS MADRE DE GRASA DE RATONES JOVENES SOBRE PARAMETROS DE ENVEJECIMIENTO Y FRAGILIDAD EN RATONES DE EDAD AVANZADA/ Reproducció del document publicat a: https://doi.org/10.1111/acel.14429 Aging Cell, 2025. vol. 24, num. 4, e14429 https://doi.org/10.34810/data1748 info:eu-repo/grantAgreement/EC/H2020/696295/EU/ERA-HDHL info:eu-repo/grantAgreement/EC/H2020/825546/EU/DIABFRAIL-LATAM cc-by (c)The Authors, 2024 Attribution 4.0 International info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/4.0/ Anatomical Society John Wiley & Sons