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Caloric restriction decelerates premature aging and cognitive decline in mice with deficient DNA repair.

Overview

Authors: Chris Z Wei1,2, Yejie Shi1,2, Wenting Zhang1,2, Sulaiman H Hassan1,2, Ruyu Shi2,3, Hongjian Pu1,2, Hongfeng Mu2, R Anne Stetler1,2, Rehana K Leak4, Jun Chen1,2
ORCID iDs: Yejie Shi, Wenting Zhang, Ruyu Shi, Hongjian Pu, Rehana K Leak, Jun Chen
  1. Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA USA
  2. Center for Cerebrovascular Disease Research and Department of Neurology, University of Pittsburgh, Pittsburgh, PA USA
  3. Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA USA
  4. Graduate School of Pharmaceutical Sciences, School of Pharmacy, Duquesne University, Pittsburgh, PA USA
Institutions: University of Pittsburgh (United States); Geriatric Research Education and Clinical Center (United States); VA Pittsburgh Healthcare System (United States); Duquesne University (United States)
Journal: Communications biology, volume 9, issue 1, article 960
Dates: received 6 May 2025; accepted 23 April 2026; published online 8 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s42003-026-10182-3 · PMID 42098305 · PMCID PMC13369994 · OpenAlex W7160551007
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), cellular / molecular (subfield)
Methods: Statistics, Connectivity, Smoothing, state filtering, decompositions
Keywords: Cognitive ageing, Neural ageing
MeSH: Aging, Premature*, Caloric Restriction*, Cognitive Dysfunction*, DNA Repair*, DNA-(Apurinic or Apyrimidinic Site) Lyase*, Animals, DNA Damage, Excision Repair, Male, Mice, Mice, Knockout, Neurons (* major topic)
Topic: DNA Repair Mechanisms (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: BLRD VA (I01 BX003377, I01 BX005290); U.S. Department of Veterans Affairs (BX003377, 821-RC-NB-30556); NINDS NIH HHS (R21 NS112671)
Citations: not cited yet (Europe PMC); 69 references in the paper

Abstract

Accumulation of DNA damage, particularly oxidative DNA damage, is a major molecular driver of senescence and aging. The enzyme apurinic/apyrimidinic endonuclease-1 (Apex1) is essential for base-excision repair, but its role in protecting the brain from age-related deterioration remains unclear. Here we show that conditional knockout (cKO) of Apex1 in forebrain neurons causes early and progressive cognitive impairment in mice. Apex1 cKO mice display deficits in spatial learning and memory (8-12 weeks), alongside reduced synaptic proteins, altered neuronal morphology, and impaired long-term potentiation at 48 weeks. We further show that a 30% caloric restriction (CR) regimen at 8-48 weeks markedly attenuates these premature aging features and improves cognitive outcomes in Apex1 cKO mice. These findings confirm Apex1 as a critical genomic maintenance factor in the aging brain and highlight the Apex1 cKO model as a valuable tool for studying endogenous defenses and dietary interventions against aging.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

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Data

Datasets cited

Data availability

Microarray data are deposited in the Gene Expression Omnibus database at the National Center for Biotechnology Information (GSE324956 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324956) and GSE297212 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE297212)). All other relevant data supporting the findings are available within the paper and the Supplementary Materials. Source data used for generating the plots are available in the Supplementary Data file associated with the manuscript. Additional information and reagents are available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 2 keywords, 12 MeSH terms, 3 funders, 69 references.

Cite

This paper

Wei, C. Z., Shi, Y., Zhang, W., Hassan, S. H., Shi, R., Pu, H., Mu, H., Anne Stetler, R., Leak, R. K., & Chen, J. (2026). Caloric restriction decelerates premature aging and cognitive decline in mice with deficient DNA repair. Communications biology, 9(1), 960. https://doi.org/10.1038/s42003-026-10182-3

BibTeX

@article{wei2026caloric,
author = {Wei, Chris Z and Shi, Yejie and Zhang, Wenting and Hassan, Sulaiman H and Shi, Ruyu and Pu, Hongjian and Mu, Hongfeng and Anne Stetler, R and Leak, Rehana K and Chen, Jun},
title = {{Caloric restriction decelerates premature aging and cognitive decline in mice with deficient DNA repair}},
journal = {Communications biology},
year = {2026},
month = may,
volume = {9},
number = {1},
pages = {960},
publisher = {Nature Publishing Group},
issn = {2399-3642},
doi = {10.1038/s42003-026-10182-3},
url = {https://doi.org/10.1038/s42003-026-10182-3},
pmid = {42098305},
pmcid = {PMC13369994}
}

RIS

TY - JOUR
AU - Wei, Chris Z
AU - Shi, Yejie
AU - Zhang, Wenting
AU - Hassan, Sulaiman H
AU - Shi, Ruyu
AU - Pu, Hongjian
AU - Mu, Hongfeng
AU - Anne Stetler, R
AU - Leak, Rehana K
AU - Chen, Jun
TI - Caloric restriction decelerates premature aging and cognitive decline in mice with deficient DNA repair
T2 - Communications biology
J2 - Commun Biol
PY - 2026
DA - 2026/05/08
VL - 9
IS - 1
SP - 960
SN - 2399-3642
PB - Nature Publishing Group
DO - 10.1038/s42003-026-10182-3
UR - https://doi.org/10.1038/s42003-026-10182-3
LA - en
ER -

CSL-JSON

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