Evidence map›Paper›PMID 42764338›Full record

ArticleNature communications2026

Sex-specific trajectories of nonlinear immune aging at single-cell level.

Harry Park, Nina Le Bert, Antonio Bertoletti, Nicholas Tolwinski, Jan Gruber, Jacques Behmoaras

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

6 authors.

Harry ParkCentre for Biomedical Data Science, Duke-NUS Medical School, Singapore, Singapore.ORCID http://orcid.org/0009-0004-0376-2913
Nina Le BertProgram in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.ORCID http://orcid.org/0000-0003-0502-2527
Antonio BertolettiProgram in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.ORCID http://orcid.org/0000-0002-2942-0485
Nicholas TolwinskiProgram in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore.ORCID http://orcid.org/0000-0002-8507-2737
Jan GruberHealthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Jacques BehmoarasCentre for Biomedical Data Science, Duke-NUS Medical School, Singapore, Singapore. jacquesb@duke-nus.edu.sg.ORCID http://orcid.org/0000-0002-5170-2606

Funding

Agency for Science, Technology and Research (A*STAR) H24J4a0019Ministry of Education - Singapore (MOE) MOE-T2EP30125-0010MOH | National Medical Research Council (NMRC) OFIRG24jan-0083MOH | National Medical Research Council (NMRC) OFLCG22may-0011
6 · The paper itself

Abstract

Despite the female predominance in age- and immune-associated diseases, the pathways underlying sex differences in healthy immune aging remain incompletely understood. Here, we analyze a multi-ethnic single-cell transcriptome of healthy human immune aging (35% Asian), comprising 3.8 million peripheral blood mononuclear cells (PBMCs) from 1,828 individuals aged 19-97 years. Prominent peaks of differential gene expression around 40 (mainly CD4 T cells) and after 60 (mainly CD8 T cells) years of age were accompanied by an age-dependent decline in RNA/protein homeostasis and inflammatory PBMC polarization with sex-dependent kinetics. While females displayed sustained CD8 T cell activation and late-life aging signatures in CD4 T, NK, and B cells, males exhibited early-life fluctuations in CD4 T cell immunometabolism associated with hypomethylation of SSH3 at chromosome 11q13. Deep learning-based biological age clocks stratified for sex outperformed sex-combined models, learning from transcriptional immune trajectories. We thus unravel a nonlinear PBMC aging whereby targeting sex-specific pathways might allow precision geromedicine.

Indexed as

AgingAdultAgedAged, 80 and overCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesFemaleHumansLeukocytes, MononuclearMaleMiddle AgedSex CharacteristicsSex FactorsSingle-Cell AnalysisSingle-Cell Gene Expression AnalysisTranscriptome

Identifiers

PMID42764338
PMCPMC13590653

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.