Evidence map›Paper›PMID 42463951›Full record

ArticleNature aging2026

Trained immunity links hematopoietic stem cell aging to aging-associated inflammation.

Wei-Chieh Mu, Marine Barthez, Yufan Feng, Yibing Chen, Chih Ling Wang, Jing-Yi Huang, Jie Li, Paul Lanhart, K Claire Tsuei, Yang Joon Kim and 3 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature aging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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

5 · Who and what money

Authors and funding

13 authors.

Wei-Chieh Mu *Department of Metabolic Biology and Nutrition, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-2669-7312
Marine Barthez *Department of Metabolic Biology and Nutrition, University of California, Berkeley, CA, USA.
Yufan Feng *Department of Metabolic Biology and Nutrition, University of California, Berkeley, CA, USA.
Yibing Chen *Department of Metabolic Biology and Nutrition, University of California, Berkeley, CA, USA.
Chih Ling Wang *Department of Metabolic Biology and Nutrition, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-0836-5026
Jing-Yi HuangBuck Institute for Research on Aging, Novato, CA, USA.
Jie LiBioinformatics Core, University of California, Davis, CA, USA.ORCID http://orcid.org/0000-0001-9522-0097
Paul LanhartActive Motif, Carlsbad, CA, USA.
K Claire TsueiDepartment of Metabolic Biology and Nutrition, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0009-0002-9179-0345
Yang Joon KimChan Zuckerberg Biohub, San Francisco, CA, USA.
Eric VerdinBuck Institute for Research on Aging, Novato, CA, USA.ORCID http://orcid.org/0000-0003-3703-3183
Mihai G NeteaDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands. mihai.netea@radboudumc.nl.ORCID http://orcid.org/0000-0003-2421-6052
Danica ChenDepartment of Metabolic Biology and Nutrition, University of California, Berkeley, CA, USA. danicac@berkeley.edu.ORCID http://orcid.org/0000-0001-9169-4973

Funding

Inflammation and Aging-associated DiabetesR01AG063389 · NIA · UNIVERSITY OF CALIFORNIA BERKELEY · PI CHEN, DANICA · 2019 to 2023
$2.0M
Nutrient Sensing, Hematopoietic Stem Cell Metabolism and AgingR01AG063404 · NIA · UNIVERSITY OF CALIFORNIA BERKELEY · PI CHEN, DANICA · 2018 to 2022
$2.0M
Hematopoietic Stem Cell AgingR01DK117481 · NIDDK · UNIVERSITY OF CALIFORNIA BERKELEY · PI CHEN, DANICA · 2018 to 2021
$1.7M
Neural Stem Cell Aging and NeurodegenerationR01AG082105 · NIA · UNIVERSITY OF CALIFORNIA BERKELEY · PI DANICA CHEN · 2024 to 2026
$1.7M
NIA NIH HHS R01 AG063389NIA NIH HHS R01 AG063404NIA NIH HHS R01 AG082105NIDDK NIH HHS R01 DK117481U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01AG063389U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01AG063404U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01AG082105U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01DK117481
6 · The paper itself

Abstract

Trained immunity is a state of heightened immune response that is initiated in hematopoietic stem cells (HSCs) and mediated mainly by their myeloid progeny. Aging-associated inflammation drives many aging-related diseases, yet its biological origin is largely unknown. Here we show that SIRT3, a mitochondrial deacetylase highly expressed in HSCs but reduced during aging, suppresses the HSC response to aging that drives maladaptive trained immunity, chronic inflammation and tissue functional decline in mice. Overexpression of SIRT3 in HSCs not only ameliorates aging-associated HSC decline, but also improves the function of distant tissues, including attenuation of age-related declines in cognition and motility, via myeloid cells with modulated inflammatory programs. These findings reveal that HSC aging is a driver of aging-associated inflammation through maladaptive trained immunity and broaden the possible clinical applications of targeting HSCs from hematological diseases to include countering aging-associated physiological decline and improving healthspan.

Indexed as

AgingCellular SenescenceHematopoietic Stem CellsInflammationTrained ImmunityAnimalsMiceMice, Inbred C57BLSirtuin 3Sirtuin 3

Identifiers

PMID42463951
PMCPMC13573651

What OpenQuestion holds

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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 OpenQuestion graph.