Evidence map›Paper›PMID 39639682›Full record

ArticleAging cell2025

Phenotypic upregulation of hexocylceramides and ether-linked phosphocholines as markers of human extreme longevity.

Anna Fernàndez-Bernal, Joaquim Sol, José Daniel Galo-Licona, Natàlia Mota-Martorell, Cristina Mas-Bargues, Ángel Belenguer-Varea, Èlia Obis, José Viña, Consuelo Borrás, Mariona Jové and 1 more

Abstract read
In one paragraph

Article in Aging cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Anna Fernàndez-BernalDepartment of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain.
Joaquim SolDepartment of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain.ORCID 0000-0003-1424-8958
José Daniel Galo-LiconaDepartment of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain.
Natàlia Mota-MartorellDepartment of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain.
Cristina Mas-BarguesFreshage Research Group, Department of Physiology, Faculty of Medicine, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable-Instituto de Salud Carlos III (CIBERFES-ISCIII), Institute of Health Research-INCLIVA, University of Valencia, València, Spain.
Ángel Belenguer-VareaDivision of Geriatrics, Hospital Universitario de La Ribera (Alzira, Valencia, Spain), School of Doctorate, Universidad Católica de Valencia, Valencia, Spain.
Èlia ObisDepartment of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain.ORCID 0000-0002-6838-1634
José ViñaFreshage Research Group, Department of Physiology, Faculty of Medicine, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable-Instituto de Salud Carlos III (CIBERFES-ISCIII), Institute of Health Research-INCLIVA, University of Valencia, València, Spain.ORCID 0000-0001-9709-0089
Consuelo BorrásFreshage Research Group, Department of Physiology, Faculty of Medicine, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable-Instituto de Salud Carlos III (CIBERFES-ISCIII), Institute of Health Research-INCLIVA, University of Valencia, València, Spain.
Mariona JovéDepartment of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain.ORCID 0000-0001-5577-6162
Reinald PamplonaDepartment of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain.

Funding

Conselleria d'Educació, Investigació, Cultura i Esport CIAICO/2022/190Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya 2021SGR00990Diputació de Lleida PP10605-PIRS2021Diputació de Lleida PP10845-PIRS2023Horizon 2020 Framework Programme 696295Horizon 2020 Framework Programme 825546Instituto de Salud Carlos III AC20/00026Instituto de Salud Carlos III CB16/10/00435 (CIBERFES)Instituto de Salud Carlos III PI24/01431Ministerio de Ciencia y Tecnología PID2020-113839RB-I00Ministerio de Ciencia y Tecnología PID2023-152233OB-I00
6 · The paper itself

Abstract

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.

Indexed as

CeramidesLongevityPhosphatidylcholinesUp-RegulationAgedAged, 80 and overBiomarkersFemaleHumansLipidomicsMalePhenotypeBiomarkersCeramidesPhosphatidylcholinescentenarianscententarians' offspringether lipidsextreme longevityhexocylceramideslipidomics

Identifiers

PMID39639682
PMCPMC11984674

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.